Title of Invention	"ANTI-EXTENDED TYPE I GLYCOSPHINGOLIPID ANTIBODY AND DERIVATIVES THEREOF"
Abstract	Human antibodies and antigen-binding portions of those antibodies that specifically bind extended Type I chain glycosphingolipids are provided.

Full Text

FORM 2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENTS RULES, 2003 COMPLETE SPECfFfCAnOtf [See section 10, Rule 13] ANTI-EXTENDED TYPE I GLYCOSPHINGOLIPID ANTIBODY, DERIVATIVES THEREOF AND USE; GLYCONEX INC., A CORPORATION ORGANIZED AND EXISTING UNDER THE LAWS OF TAIWAN, WHOSE ADDRESS IS 11F„ NO. 31-1, LANE 169, KANG-NING ST., HSI-CHIH DIST., NEW TAIPEI CITY 22180, TAIWAN. THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BP PERFORMED. Tong-Hsuan Chang, Jerry Ting, Tsai-Hsia Hong. Mei-Chun Yang, Liahng-Yirn Lin, Shu-Yen Chang, Ying-Zin Chen, Jaw-Yuan Wen, Kazuko Handa and Sen-itiroh Hakomori FIELD OF THE INVENTION The present invention relates to anti-extended Type I glycosphingolipid antibodies and their use in the amelioration, treatment or prevention of diseases or disorders in mammals, including humans, resulting from improper activity or metabolism of same; resulting, causing or associated with; or the presence thereof, for example, in a cancer, such as colorectal cancer, or other pathology. An antibody of interest can be used for therapeutic purposes or diagnostic purposes. Thus, prophylactic, immunotherapeutic and diagnostic compositions comprising the antibodies and derivatives thereof of interest and their use in methods for preventing or treating, or diagnosing diseases in mammals, including humans, caused by inappropriate metabolism and/or expression of extended Type I glycosphingolipid in and on ceils, such as certain malignant cells, also are disclosed. BACKGROUND [Extended Type 1 glyeosphingoiipid is a cell surface molecule that can be associated with, for example, certain malignant states. Aberrant glycosylatioo has been observed to be a common feature of many cancer types, Hakomori, PNAS 99:10231-10233, 2002. Some of the carbohydrate antigens used for the diagnosis of human cancers carry poiytactosamine structures, Polyiactosamines are usually classified into two categories according to the unit structure. A polylactosamine having the Galβl →3G1 cNAc structure is called a Type I chain, and that having the Galβl →4G1 c'NAc structure is referred to as a Type 1 I chain. The most common tumor-associated antigens found in some human cancers have the lacto series Type n chain structure, which usually is sialylated and/or fucosylated. Type 1 chain antigens are abundant in normal cells and tissues, and occasionally are associated with cancer, Stroud et al., JBC 266: 8439-8446, 1991. for example, 2→3 sialylated Lea antigen (the CA 19-9 antigen defined by the N19-9 antibody) is a cancer-associated Type I chain antigen. However, cancer diagnostic methods based on the detection of those Type ] antigens have been hampered by high false positive and/or high false negative incidences, see, for example U.S. Patent Nos. 6,083,929 and 6,294,523. Two mouse monoclonal antibodies, NCC-ST421 and IMH2, were raised against extended Type I chain antigens. NCC-ST421 is specific for Le3-Le3. The NCC-ST421 antibody strongly induced antibody dependant cell cytotoxicity (ADCC) using human peripheral blood leukocytes as effectors against a variety of human tumor cells, and induced complement dependent cytotoxicity (CDC) with a human complement source. Watanabe et a!., Cancer Res. 51:2199-2204,1991 The Le'-Le" antigen was found to be highly expressed in the human colon carcinoma cell line, Colo205. IMH2 was also established against extended Type 1 chains. IMH2 bound to Lch-Le, Ley-Lex Leh and I,ey based on 'H-NMR, FAB-MS and enzymatic degradation studies. Stroud et a!., Eur. J. Biochem. 203:577-586, 1992. 1MH2 showed strong lymphocyte-activated, as well as, complement-dependent killing of Colo20S cells in vitro, and inhibited Coio205 growth in vivo. 1MH2 reacted with carcinoma tissues derived from colon, pancreas, liver and endometrium. However, normal colon showed no reactivity with IMB2. Normal liver and pancreas showed weak or highly restricted reactivity in normal hepatocytes and islets of Langerhans cells. Immunochemical staining intensity was much stronger in endometrial carcinomas than in norma! endometrium, Ito etal., Cancer Res. 52:3739-3745, 1992. Both NCC-ST421 and IMH2 exhibit inhibition of tumor growth in nude mice after inoculation of human tumor cells expressing the extended Type [ chain antigen, but no inhibition of growth occurred in tumor ceils that did not express extended Type I chain antigen. Because of the abundance of Type I structures on normal cells, the use of Type I antibodies for diagnostic and/or therapeutic purposes heretofore was not possible. Conventional cancer treatments, such as chemotherapy and radiotherapy, have shown some advantages in various cancer patients. Despite the benefits of antitumor activity in conventional therapies, however, treatment-induced toxicity to normal tissues can substantially reduce the quality of life in cancer patients. Dose intensification for belter antitumor activity is also limited. Monoclonal antibodies enable the promise of targeted cytotoxicity, focusing on tumor tissues, but not normal tissues. Monoclonal antibodies (mAbs} can be developed with high specificity for antigens expressed on tumor cells and can elicit desired antitumor activities. The promise of ntAbs was furthered by the development of mice that produce fully human mAbs. One such tool is the KM mouse, U.S. Pa! No. 7,041.870 and Tomizuka et al..Nat. Genet. 16:133-143, .1997. In the KM mouse, the mouse genes encoding immunoglobulins were inactivated and replaced with human antibody-genes. Thus, the KM mouse expresses fully human antibodies. Several fully human antibodies have been successfully developed using the KM mouse. Rir example, Motoki et al. developed a human IgG (KMTR2) which directed antibody dependent oiigomerization of TRAIL-R2 and initiated efficient apoptotic signaling and tumor regression independent of host effector function (Clin. Cancer Res. 11 (8):3126-3135, 2005; and see U.S. Pot. No. 7,115,717 and Imakire el a!., Int. J. Cancer 108:564-570, 2004). H.D8, a fully human monoclonal antibody specific for human leukocyte antigen DR (HLA-DR), exerted antibody-dependent cellular cytotoxicity (ADCC) as well as complement-dependent cytotoxicity (CDC) in vitro, and extended the life span of immunocompromised mice inoculated with non-Hodgkin lymphoma cell lines, I'awara et ill., CanCer Sci. 98 (6) 921-928, 2007. Additionally, two human IgMs raised in KM mke and directed to carbohydrate antigens were reported. HMMC-1 specifically recognizes a novel O-glycan structure. reacts positively with Multe-rian duct-related carcinomas, and exhibits complement dependent cytotoxicity on a human uterine endometrial cancer cell line, SNG-S, Nozawa et at., Clin Cancer Res. 10:707 1-7078,2004. Another human monoclonal IgM, HMOCC-1, recognizing a glycoprotein located on the cell membrane, reacted with ovarian cancel (Suzuki et al, Gynecol. Oncol. 95:290-298, 2004). Since those two antibodies are IgMs. the application of those antibodies in cancer therapy should be limited by molecule sixe ane{ restrictions in production. SUMMARY and derivatives thereof, that specifically bind to extended Type 1 giycosphingolipid. The invention includes the amino acid sequences of the variable heavy and light chain of the antibodies and their corresponding nucleic acid sequences. Another embodiment of the invention includes the complementarity determining regions (CDR) sequences of the antibod.ies of interest to obtain binding molecules that comprise one or more CDR regions, or CDR-derived regions, that retain extended. Type I glycosphingolipid-btnding capacity of the parent molecule ■from which the CDR's were obtained. Another embodiment of the present invention includes the cell lines and vectors harboring the antibody sequences of (he preset, invention. Another embodiment of the present invention relates to the use of the antibodies for the preparation of a medicament or composition for the treatment of diseases and disorders associated with extended Type | glycosphingolipid function. metabolism and expression. Another embodiment of the present invention relates to die use of the antibodies in the diagnosis of disorders associated with atypical or abnormal extended Type 1 glycosphingolipid biology and expression. Those and other goals were met in the development of human monoclonal antibodies against extended Type I chain carbohydrate antigens. For example, mAb GNX-8 is a human lgGl derived from a KM mouse. GNX-8 exhibits CDC and ADCC activity on several human colorectal cancer cell lines and inhibits Colo205 and DLD-1 tumor growth in vivo. GNX-8 reacts with primary and metastatic colorectal cancers, breast cancers,, pancreas cancers as well as lung cancers, but not with normal human tissues and blood cells. Additional features and advantages are described herein, and will be apparent from, the following Detailed Description. DETAILED DESCRIPTION The invention is not limited to the particular methodology, protocols, polypeptides, polynucleotides, cell lines, vectors, or reagents described herein because variations can occur or can be used without departing from the spirit and scope of tire invention. Further, die terminology used herein is for the purpose of exemplifying particular embodiments only and is not intended to limit the scope of the present invention. Unless defined otherwise, all technical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of the invention. Any method and material similar or equivalent to those described herein can be used in the practice of the present invention and only exemplary methods, devices, and materials are described herein. All patents and publications mentioned herein are incorporated herein in entirety by reference for the purpose of describing and disclosing the proteins, enzymes, vectors, host cells and methodologics reported therein that might be used with and in the present invention. However, nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosures by virtue of prior invention. An "extended Type I giycosphingolipid disease" is a malady, disorder, disease, pathology, condition, abnormality ami so on, which is characterised by. associated with or caused by abnormal metabolism , overexpression or increased .levels of extended Type I giycosphingolipid, for example, at the eel! surface. The phrase "substantially identical" with respect to an antibody polypeptide sequence may be constated as an antibody chain exhibiting at least 70%, 80%, 90%, 95% or more sequence identity to a reference polypeptide sequence. The term with respect to a nucleic acid sequence may be construed as a sequence of nucleotides exhibiting at least about 85%, 90%, 95%, 97% or more sequence identity to a reference nucleic acid sequence. The terms, "identity" or "homology" may mean the percentage of (tacleattde bases or amino scid residues in (he cmdidntc sequence that is identical with the residues of a corresponding sequence to which. the candidate is compared, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity for the entire sequence, and not considering any conservative substitutions as part of the sequence identity. Neither N-terminai nor C-terminai extensions nor insertions shall be construed as reducing identity or homology. Methods and computer programs for the alignment of sequences are available and are well known in the art. Sequence identity may be measured using sequence analysis software. The phrases and terms, "functional fragment, variant, derivative or analog" and the like, as well as forms thereof, of an antibody, nucleic acid or antigen is a compound or molecule having qualitative biological activity in common with a full length antibody or antigen of interest. For example, a functional fragment or analog of an anti-extended Type i giycosphingolipid antibody is one which can bind to fin extended Type I giycosphingolipid molecule, or is an agonistic or antagonistic antibody which binds to extended Type I giycosphingolipid. Art example is an seFv molecule. As to extended Type I giycosphingolipid, a variant of derivative thereof is a molecule that is not identical to a naturally occurring extended Type I glycosphingolipid and yet can be used for a purpose of the instant invention, such as, while not identical to a wild type extended Type I glycosphingolipid nevertheless can be used, for example, as immunogen to raise antibodies that selectively bind to wild type extended Type I glycosphingolipid. "Substitutional" variants are those that have at least one amino acid residue in a native sequence removed and replaced with a different amino acid inserted in place at the same position. The substitutions may be single, where only-one amino acid in the molecule is substituted, or may be multiple, where two or more amino acids are substituted in the same molecule. The plural substitutions may be at consecutive sites. Also, one amino acid can be replaced with plural residues, in which case such a variant comprises both a substitution and an insertion. "Insertional" variants ate those with one or more amino acids inserted immediately adjacent to an amino acid at a particular position in a native sequence. immediately adjacent to an amino acid means connected to either the a-carboxyl or α-amino functional group of the amino acid. "Deletional" variants are those with one or more amino acids in the native amino acid sequence removed. Ordinarily, deletional variants will have one or two amino acids deleted .in a particular region of the molecule. The terms, substitution, insertion and deletion variants also apply analogously to nucleic acids. The adaptive immune response has two major arms: the cellular immune response of T lymphocytes and the humoral immune response of antibody secreting \i lymphocytes. B cell epitopes caw be linear, contiguous amino acids, or can be conformational (Protein Science (2005) 14. 246). In contrast T cell epitopes are short linear peptides that are cleaved from antigenic proteins that are presented in the context of major histocompatibility complex (MHC) proteins, or, in case of humans, human leukocyte antigen (H.LA) class I or class 33 molecules. Epitope presentation depends on both MHC-peptide binding and T cell receptor (TCll) interactions. MHC proteins are highly polymorphic, and each binds to a limited set of peptides. Thus, the particular combination of MBC alleles present in a host limits the range of potential epitopes recognized during an infection. Two fundamental types of T cells are distinguished by expression of CDS and CD4 proteins, which dictate whether a T cell will recognize epitopes presented by class I or class II molecules, respectively. CD4 T epitopes are processed after encapsulation by antigen presenting cells in membrane bound vesicles, where the antigen is degraded by proteases into peptide fragments that bind to MHC class II proteins. In contrast, CD8' T cells generally recognize viral or self antigens expressed from within a cell, proteins that are cleaved into short peptides in the cytoaol by the immunoproteasome. After cleavage, peptides are translocated by the transporter associated with antigen processing (TAP) into the endoplasmic reticulum for loading onto H.LA I. antigens. CD4T (helper) cell epitopes are critical in driving T cell-dependent immune responses to protein antigens. The term "antibody" is used in the broadest sense, and includes monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), antibody fragments or synthetic polypeptides carrying one or more CDR or CDR-derived sequences so long as the polypeptides exhibit the desired biological activity. Antibodies (Abs) and immunoglobulins (Igs) are glycoproteins having the same structural characteristics. Generally .antibodies are considered Igs with a defined or recognized specificity. Thus, while antibodies exhibit binding specificity to a specific, target; immunoglobulins include both antibodies and other antibody-like molecules which lack target specificity. The antibodies of the invention can be of any class (e.g., JgG, Igli, IgM, IgD, IgA and so on), or subclass (e.g., IgGt. IgG3, IgG3.-,, IgG.?, IgG4, lgASl IgA2 and so on) ("type" and "class." and "subtype" and ""subclass/* are used interchangeably herein). Native or wildtype, that is, obtained from a non-artificially manipulated member of a population, antibodies and immunoglobulins, and monomers of polymeric antibodies, such as IgA and EgM, are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each heavy chain has at. one end a variable domain (VH) followed by a number of constant domains. Each light chain has a variable domain at one end (V1.) and a constant domain at the other end. By "non-artificially manipulated" is meant not treated by non-natural means, such as immunization or transformation, to contain or to express a foreign antigen binding molecule. Wildtype can refer to the most prevalent allele or species found in a population or to the antibody obtained from a non-artiftc tally manipulated animal, as well as to naturally occurring alleles or polymorphisms which arise naturally and can he sustained in a population, or a variant or derivative arising through natural means, such as a malignancy, as compared to that obtained by a form of manipulation, such as mutagenesis, use of recombinant methods and so on to change an amino acid of the ami gen-binding molecule. The use of the term is readily inferred and understood by the artisan in die context of the sentence, paragraph, concept, diought, idea and so on in which the term is found, used and so on.. As used herein, "anti-extended Type 1 glycosphingolipid antibody" means an antibody or derived polypeptide which binds specifically to human extended Type f glycosphingolipid. [0038] The term "variable" in the context of a variable domain of antibodies, refers to certain portions of a pertinent molecule which differ extensively in sequence between and among antibodies and can be integral in the specific recognition and binding of a particular antibody to a particular target. However, the variability is not evenly distributed through the variable domains of antibodies. The variability can be concentrated in three segments called complementarity determining regions (CDRs; i.e., CDR.1, CDR2 and CDR3) also known as hypervariable regions, both in the light chain and the heavy chain variable domains. The more highly conserved portions of variable domains are called the framework (FR) regions or sequences. The variable domains of native heavy and light chains each comprise four .FR regions, largely adopting a C3 sheet configuration., connected by three CDRs, which form loops connecting, and in some cases forming part of, the p sheet structure. The CDRs in each chain are held together, often in proximity, by the FR regions and, with the CDRs from the other chain, contribute to the formation of the target (epitope or detenuinant) binding site of antibodies (see Kabat et al. Sequences of Proteins of Immunological interest. National Institute of Health, Bethesda, MD (1987)). One CDR, such as, CDR3 of the heavy chain, can alone carry the ability to bind specifically to the cognate epitope. As used herein, numbering of immunoglobulin amino acid residues is done according to the immunoglobulin amino acid residue numbering system of Kabat et al, unless otherwise indicated. The term "antibody fragment" refers to a portion of an intact or a full length chain of an antibody, generally the target binding or variable region. Examples of antibody fragments include, but are not limited to, Fab, Fab-. F(ab',2 and Fy fragments. A "functional fragment'' or "analog of an ami-extended Type I glycosphsngolipid antibody' is one which can bind a cognate antigen . As used herein, functional, fragment generally is synonymous with, "antibody fragment," and with respect to antibodies, can refer to fragments, such as Fv. F9b, F(ab) and so on which can bind a cognate antigen. An "Fr" fragment consists of a ditner of one heavy and one light chain variable domain in a non-covalem association (V|f1-V1, tltmer). That configuration of the three CDR's of each variable domain interact to define a target binding site of the VH-V1 dimer as in an intact antibody. Collectively, the six CDRs confer target binding specificity on the intact antibody. However, erven a single variable domain (or half of an Fv comprising only three CDRs specific for a target) can have the ability to recognize and to bind target. "Single-chain FV" "sFv" or "scA'b" antibody fragments comprise the V'H and V'L domains of an antibody, wherein the domains ate present in a single polypeptide chain. Generally, the Fv polypeptide further comprises a polypeptide linker, often a flexible molecule, such as. an oligopeptides, which may be obtained from a naturally occurring molecule, derived from a naturally occurring molecule, is an artificial sequence, such as polyglycine, and so on, between the Vn and V1 domains, which enables the sFv to form the desired structure for target binding, Some molecules can include one or more constant domains or a portion thereof. The term "diabodies" refers to antibody fragment constructs with two antigen binding sites, which fragments can comprise a heavy chain variable domain (VH) connected to a light chain variable domain (Vi„) in the same polypeptide chain. By using a linker that is too short to allow pairing between the th the binding domains of another chain to create an antigenwo variable domains on the same chain, the diabody domains are forced to pair wit binding site. The Fab fragment contains the variable and constant domains of the light chain and the variable and first constant domain (Cm) of the heavy chain. Fab-fragments differ from F3b fragments by die addition of a few residues at the carboxyl terminus of the CH1 domain to include one or more cysteines from the antibody hinge region, Fah- fragments can be produced by cleavage of the disulfide bond at the hinge cysteines of the F(ab) pepsin digestion product. Additions} enzymatic and chemical treatments of antibodies can yield other functional fragments of interest. lire term "monoclonal antibody" (mAb or MAb) as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies herein specifically include "chimeric" antibodies in which a portion of the heavy and/or light, chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass (type or subtype), with the remainder of the cluun(s) identical with or homologous to corresponding sequences iii antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as the chimeric antibodies exhibit the desired biological activity of binding to extended Type I glycosphingolipid or impacting extended Type I glycosphingolipid activity or metabolism (U.S. Pal No. 4,816,567; and Morrison et al., Proc Natl Acad Set USA 81:6851 (1984)). Thus. CDR's from one class of antibody can be grafted into the FR of asi antibody of different class or subclass. Monoclonal antibodies are specific, being directed against a single target site, epitope or determinant. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes) of an antigen, each monoclonal antibody is directed against a single determinant on the target. In addition to their specificity, monoclonal antibodies are advantageous being synthesized by a host celt, uncontaminated by other immunoglobulins, and provide for cloning the relevant gene and mRMA encoding the antibody chains thereof. The modifier "monoclonal" indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibadies for use with the present invention may be isoated front phage antibody libraries using well known techniques or can be purified from a polyclonal prep. The parent monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method described by Kolner et al, Nature 256:495 (1975), or may be made by recombinant methods well known in the art. "Humanized" forms of non-human (e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments diereof (such as fv, F;!(), F,*-, F(AB): or othyr target-binding subsequences of antibodies) which contain sequences derived from non-human immunoglobulin, as compared to a human antibody. In general, the humanized antibody will comprise substantially all of one, and typically two, variable domains, in which all or substantially ail of the CDR. regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin template sequence. The humanized antibody may also comprise at least a portion of an immunoglobulin constant region (F,), typically that of the human immunoglobulin template chosen. In general, the goal is to have an antibody molecule of certain specificity that is minimally immunogenic in a human. Thus, it is possible that one or more ammo acids in one or wore CDR's also can be changed to one that is less immunogenic to a human host, without substantially minimizing the specific binding function of the one or more CDR's to extended Type I giycosphingoiipid. Alternatively, the FR can be non-human but those amino acids most immunogenic are replaced with ones less immunogenic. Nevertheless, CDR grafting, as discussed above, is not the only way to obtain a humanized antibody. For example, modifying just the CDR regions may not be sufficient to optimize an antibody as it is not uncommon for framework residues to have a role in determining the overall three-dimensional structure of the CDR loops and the overall affinity of the antibody for the ligand. Hence, any means can be practiced to reduce antibody iramunogenicity so that the non-human parent antibody molecule is modified to be one that is less immunogenic to a human, and global sequence identity with a human antibody is not always s necessity. So, humanization also can be achieved, for example, by the mere substitution of just a few residues, particularly those which are exposed on the antibody molecule surface and not buried within the molecule, and hence, not readily accessible- to the host immune system. Such a method is taught herein with respect to substituting, for example, charged or certain other residues on the antibody molecule, the goal being to reduce or dampen the immimogenicity of the resultant molecule without compromising the specificity of the antibody for the cognate epitope or determinant. See, for example. Stuclnicka et. al., Prot Eng 7(6)805-814, 1994; Mo! Iram 44:1986-1988,2007; Sims el al, J Immunol 151:2296 (1993); Chothia etal., i Mol Biol 196:901 (1987); Carter ei al„ ProcNatl Acad Sci USA 89:4285 (1992): Presto ei al., J Immunol 151.2623 (1993), WO 2006/042333 and U.S. Pat. No. 5.869,619. Strategies and methods for resurfacing antibodies, and other methods for reducing umnunogenicity of antibodies within a different host; are disclosed, for example, in U.S. Pat. No. 5,659,641. Briefly, in a preferred method, (1) position alignments of a pool of antibody heavy and light chairs variable regions are generated to yield heavy and light chain variable region framework surface exposed positions, wherein the alignment positions for all variable regions are at least about 98% identical; (2) a set of heavy and light chain variable region framework surface exposed amino acid residues is defined for a non-human, such as, a rodent antibody (or fragment thereof); (3) a set of heavy and tight chain variable region framework surface exposed amino acid residues that is most closely identical to the set of rodent surface exposed amino acid residues is identified; and (4) the set of heavy and light chain variable region framework surface exposed amino acid residues defined in step (2) is substituted with die set of heavy and light chain variable region framework surface exposed amino acid residues identified in step (3), except for those amino acid residues that are within about 5 A of any atom of any residue of a CDR of the, for example, rodent antibody, to yield a humanized, such as. a rodent antibody retaining binding specificity. Antibodies can be humanized by a variety of other techniques including CDR grafting (EPO 0 239400; WO 91/09967; and U.S. Pat. Nos. 5,530,103 and 5,585,089), veneering or resurfacing (EPO 0 592 106; EPO (! 519 596; Padlan\ .1991, Molec Imm 28(4/5):489-498: Studnicka et aL 1994, Prot Eng 7(6):805-814; and Roguska el al., 1994, PNAS 91 ;969-973) and chain shuffling (U.S. Pat. No. 5,565,332). Human antibodies can be made by a variety of methods known in the art including, but not limited to. phage display methods, see U.S. Pat. Nos. 4,444,887,4,716,111, 5,545,806 and 5,814,318; and WO 98/46645, WO 98/50433, WO 98/24893, WO 98/16654, WO 96/34096. WO 96/33735 and WO 91/10741, using transgenic animals, such as rodents (Arogert, K.irin and Merdarex mice), using chimeric cells and so on. "Antibody homolog' or "homolog" refers to any molecule which specifically binds extended Type i glycosphingoiipid as taught, herein. Thus, an antibody homolog includes native or recombinant antibody, whether modified or not, portions of antibodies that retain the biological properties of interest, such as binding extended Type 1. glycosphingoiipid. such as an Fat, or F, molecule, a single chain antibody, a polypeptide carrying one or more CDR regions and so on. The amino acid sequence of the homolog need not be identical to that of the naturally occurring antibody but can be altered or modified to cany substitute amino acids. inserted amino acids, deleted amino acids, amino acids other than the twenty normally found in proteins and so on to obtain a polypeptide with enhanced or other beneficial, properties. Antibodies with homologous sequences are those antibodies with amino acid sequences that have sequence homology with the amino acid sequence of an extended Type J glycosphingolipid antibody of the present invention. Preferably, homology is with the amino acid sequence of the variable regions of an antibody of the present invention. "Sequence homology" as applied to an amino acid sequence herein is defined as a sequence with at least about 90%, 91%, 92%, 93%, 94% or more sequence homology, and more preferably at least about 95%, 96%, 97%, 98% or 99% sequence homology to another amino acid sequence, as determined, for example, by the FASTA search method in accordance with Pearson & Lipman, Proc Natl Acad Set VSA 85, 2444-244$ 0988). A chimeric antibody, as taught hereinabove, is one with different portions of an antibody derived from different sources, such as different antibodies, different classes of antibody, different animal species, for example, an antibody having a variable region derived from a murine monoclonal antibody paired with a human immunoglobulin constant region and so on. Thus, a humanized antibody is a species of chimeric antibody. Methods for producing chimeric antibodies are known in the art, see, e.g.. Morrison, 1985, Science 229:1202; Oi et al, 1986, BioTechniques 4:214; Gillies et a)., 1989, .1 Immunol Methods .125:191-202; and U.S. Pat. Nos. 5,807,71.5, 4,816,5(57, and4,816,397. Artificial antibodies include scFv fragments, chimeric antibodies, diabodies, triabodies, tetrabodies and mm (see reviews by Winter & Milstein.. 1991, Nature 349:293-299; and Hudson, 1999, Curr Opin hum 11:548-557), each with antigen-binding or epitope-bitiding ability. In the single chain J\ fragment (scFv), the V'H and Vi. domains of an antibody are linked by a flexible peptide. Typically, the linker is a peptide of about \ 5 amino acids. If the linker is much smaller, for example. 5 amino acids, diabodies are formed, which are bivalent scFv dimers. If Also included within the scope of the invention arc functional equivalents of an antibody of interest. The term "functional equivalents" includes antibodies with homologous sequences, antibody homologs, chimeric antibodies, antibody variants, antibody derivatives, artificial antibodies and modified antibodies, for example, wherein each functional equivalent is defined by the ability to bind to extended Type \ glycosphingolipid. The skilled artisan will understand that there is an overlap in the group of molecules termed "antibody fragments" and the group termed "functional equivalents." Methods of producing functional equivalents which retain extended Type 1 glycosphingolipid binding ability are known to the person skilled in the art and are disclosed, for example, in WO 93/21319, EPO No. 239,400, WO 89/09622, EPO No. 338,745 and EPO No. 332,424. The functional equivalents of the present application also include modified antibodies, e.g., antibodies modified by the covalent attachment of any type of molecule to the antibody. For example, modified antibodies include antibodies that have been modified, e.g., by glycosytation, aeetyiation, peaylatiotu deamidation, phosphorylation. amidation, derivatizalion by known protecimg/blockmg groups, proteolytic cleavage, linkage to a cellular I i gaud. linkage to a toxin or cytotoxic moiety or other protein etc. Hie covalent attachment need not yield an antibody that is immune from generating an anti-idiotypic response. The modifications may be achieved by known techniques, including, but not limited to, specific chemical cleavage, aeetyiation, formyiation, metabolic synthesis, chemical conjugation etc. Additionally, the modified antibodies may contain one or more non-classical amino acids. Many techniques are available to one of ordinary skill in the art which permit die optimization of binding affinity. Typically, the techniques involve substitution of various amino acid residues at the site of interest, followed by a screening analysis of binding affinity of the mutant polypeptide for the cognate antigen or epitope. Once the antibody is identified and isolated, it is often useful to generate a variant antibody or mutant, or mutein, wherein one or more amino acid residues are altered, ibr example, in one or more of the hypervariable regions of the antibody. Alternatively, or in addition, one or more alterations (e.g., substitutions) of framework residues maybe introduced in the antibody where these result in an improvement in the binding affinity of the antibody mutant for extended Type I glycosphingolipid. Examples of framework region residues that can be modified include those which non-covaiently bind antigen directly (Amit et si... Science 233:747-753 (1986)); interact wiih/affect the conformation of a CD 11 (Chothia et a!., J. Mol. Biol. 196:901-917 (1987)); and/or participate in the V,.-VH interface (EP 239 400). In certain embodiments, modification of one or more of such framework, region residues results in an enhancement of the binding affinity of the antibody for the cognate antigen. For example, from about, one to about five framework residues may be altered in the particular embodiment of the invention. Sometimes, that may be sufficient to yield an antibody mutant suitable for use in preclinical trials, even where none of the hypervariable region residues have been altered. Normally, however, the antibody mutant can comprise one or mote hypervariable region alteration(s). The constant regions also can be altered to obtain desirable or more desirable effector properties. The hypervariable region residues which are altered may be changed randomly, especially where the starting binding affinity of the parent antibody is such that randomly-produced antibody mutants can be readily screened for altered binding in an assay as taught herein. One procedure for obtaining antibody mutants, such as, CDR mutants, is "alanine scanning mutagenesis" (Cunningham & Wells, Science 244:1081-1085 (1989); and Cunningham & Wells, Proc Nat. Acad Sci USA 84:6434-6437 (1991)). One or more of the hyper variable region residue(s) are replaced by alanine or polyalanine residues). Those hypervariabie region residue(s) demonstrating functional sensitivity to the substitutions then are refined by introducing further or other mutations at or for the sites of substitution. Thus, while the site for introducing an amino acid sequence variation is predetermined, the nature of the mutation per se need not be predetermined. Similar substitutions cart be attempted with other amino acids, depending on the desired properly of the scanned residues. A more systematic method for identifying amino acid residues to modify comprises identifying hypervariabie region residues involved in binding extended Type 3 glycosphingolipid and those hypervariabie region residues with little or no involvement with extended Type I glycosphingolipid binding. An alanine scan of the non-binding hypervariabie region residues is performed, with each ala mutant tested for enhancing binding to extended Type 1 glycosphingolipid. In another embodiment, those residue(s) significantly inv binding extended Type I glycosphingolipid are selected to be modified. Modifolved inication can involve deletion of a residue or insertion of one or more residues adjacent to a residue of interest. However, normally the modification involves substitution of the residue by another amino acid. A conservative substitution can be a first substitution. If such a substitution results in a change in biological activity (e.g., binding affinity), then another conservative substitution can be made to determine if more substantial changes are obtained. Even more substantial modification in an antibody range and presentation of biological properties can be obtained by selecting an amino acid that differs more substantially in properties from that normally resident at a site. Thus, such a substitution can be made while maintaining: (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation; (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain. For example, the naturally occurring amino acids can be divided into groups based on common side chain properties. (1) hydrophobic: methionine (M or met), alanine (A or aia), valine (V or val), leucine (L or leu) and isoleucine (i or ile); (2) neutral, hydrophilic: cysteine (C or cys), serine (S or ser), threonine (T or ihr), asparagine (N or asn) and gluiamine (Q or gln); (3) acidic: aspartic acid (D or asp) and glutamic- acid (E or gin); (4) basic: histidine (H or his), lysine (K or lys) and arginine (R. or arg); (5) residues that influence chain orientation: glycine (G or gly) and proline (P or pro), and (6) aromatic: tryptophan (W or trp), tyrosine (Y or tyr) and phenylalanine (F or phe). Non-conservative substitutions can entail exchanging an amino acid with an amino acid from another group. Conservative substitutions can entail exchange of one amino acid for another within a group. Preferred amino acid substitutions can include those which, for example: (1) reduce susceptibility to proteolysis, (2) reduce susceptibility to oxidation. (3) alter binding affinity and (4) confer or modify other physico-chemical or functional properties of such analogs, Analogs can include various muteins of a sequence other than the naturally occurring peptide sequence. For example, single or multiple amino acid substitutions (preferably conservative amino acid substitutions) may be made in the naturally-occurring sequence (preferably in the portion of the polypeptide outside the domain (s) forming inlermolecular contacts. A conservative amino acid substitution should nof substantially change the structural characteristics of the parent sequence (e. g.„ a replacement amino acid should not tend to break a helix thai occurs in the parent sequence, or disrupt other types of secondary structure that characterizes the parent sequence) unless of a change in the bulk VT conformation of theft group or side chain. Proteins, Structures and Molecular Principles (Creighton. ed., W. H. Freeman and Company, New York (1984)); Introduction to Protein Structure (Brandon & Tooze, eds.7 Garland Publishing, New York, N. Y. (1991)); and Thornton et al. Nature 354:105 (1991). Ordinarily, the antibody mutant with improved biological properties will have an amino acid sequence having at least 75% amino acid sequence identity or similarity with the amino acid sequence of either the heavy or light chain variable domain of the parent anti-human extended Type I glycosphingolipid antibody, at least 80%, at least 85%5 at least 90% and often at least 95% identity. Identity or similarity with respect to parent antibody sequence is defined herein as the percentage of amino acid residues in the candidate sequence that are identical (i.e.. same residue) or similar (i.e., amino acid residue from the same group based on common side-chain properties, supra) with the parent antibody residues, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alternatively, antibody mutants can he generated by systematic mutation of the FR and CDR. regions of the heavy and light chains, or the Fc region of the anti-extended Type I giycosphingolipid antibody. [■00S0] Another procedure for generating antibody mutants involves the use of affinity maturation using phage display (Hawkins et al., J Mot Biol 254:889-896 (1992) and Lowman et al.. Biochemistry 30(45):i0S32-1083S( 199!)). Bacteriophage coat-protein fusions (Smith, Science 228:1315 (1985); Scott & Smith, Science 249:386 (1990); Cwirla et al., Proc Natl Acad Sci USA S;?>09 (1990); Devlin et al. Science 249:404 (1990): Wells & Lowman, Curr Opin Struct. Biol 2:597 (1992); and U.S. Pat, No. 5,223,409) are known to be useful for linking the phenotype of displayed proteins or peptides to the genotype of bacteriophage particles which encode them. The Fab domains of antibodies have also been displayed on phage (McCaffetty et al., Nature 348: 552 (1990); Barbas et al. Proc Nat! Acad Sci USA 88:7978 (1991); and Garrard et al. Biotechnol 9:1373 (1991)). Monovalent phage display consists of displaying a set of protein variants as fusions of a bacteriophage coat protein on phage particles (Bass et al, Proteins 8:309 (J 990)). Affinity maturation, or improvement of equilibrium binding affinities of various proteins, has previously been achieved through successive application of mutagenesis, monovalent phage display and functional analysis (Lowman & Wells, J Mol Biol 234:564 578 (1993): and U.S. Pat. No. 5,534,617), as well as using that approach with Faf, domains of antibodies (Barbas et al., ProcNatl Acad Sci USA 91:3809 (1994); and Yang et al., J Mol Biol 254:392 (1995)). Libraries of many (for example, 106 or more) protein variants, differing at defined positions in the sequence, can be constructed on bacteriophage particles, each of which contains DNA encoding the particular protein variant. Thus, several hypervariable region sites (e.g., 6-7 sites) are mutated to generate all possible amino acid substitutions at. each she. After cycles of affinity purification, using an immobilized antigen, individual bacteriophage clones arc isolated, and the amino acid sequence of the displayed protein is deduced from the DM A. Following production of the antibody mutant, the biological activity of that molecule relative to the parent antibody can be determined as taught herein. As noted above, thai may involve determining the binding affinity and/or other biological activities or physical properties of the antibody. In a preferred embodiment of the invention, a panel of antibody mutants is prepared and is screened for binding affinity for the antigen. One or more of the antibody mutants selected from me screen are optionally subjected to one or more further biological activity assays to confirm that the antibody mufant(s) have new or improved properties. In preferred embodiments, the antibody mutant retains the ability to bind extended Type I glycosphingolipid with a binding affinity similar to or better/higher than that of the parent antibody. Alternatively, multivalent phage (McOfferty et al. (1990) Nature 348:552-554: and Clackson et at, (1991) Nature 352.624-62S) also can be used to express random point mutations (for example, generated by use of an error-prone DNA polymerase) to generates library of phage antibody fragments which then could be screened for affinity to extended Type \ glycosphingolipid, Hawkins et ai, (1992) J Mol Biol 254:889-896. Preferably, during the affinity maturation process, the replicahte expression vector is under tight control of a transcription regulatory element, and the culturing conditions are adjusted so the amount or number of particles displaying more than one copy of the fusion protein is less than about 1%. Also preferably, the amount of particles displaying more than one copy of the fusion protein is less than about 10% of the amount of particles displaying a single copy of the fusion protein. Preferably the amount is less than about 20%. Another equivalent phrase used herein is an antigen binding portion, which relates to that portion of an antibody of interest which binds a Type 1 glycosphingolipid epitope. All of the phrases and terms used herein to describe various changes that can be made to an original antibody are considered to fail within the scope of the phrase, "antigen binding potion." Hence, for example, an antibody fragment, such as, an Fab, molecule, an Fy an scAb, an mru, any such functional fragments, an antibody variant, such as an allele or a molecule containing a change in the primary amino acid sequence thereof, a derivative, such as a chimeric or humanized antibody, an analog and so on, including functional equivalents, which include genetically modified forms of an antibody of interest, antibody homologs, as described herein, and so on are included in the phrase antigen binding portion. The antibody mutants) so selected may be subjected to further modifications, often depending on die intended use of the antibody. Such modifications may involve further alteration of the amino acid sequence, fusion to heterologous polypeptide(s) and/or covalent modifications. For example, a cysteine residue not involved in maintaining the proper conformation of the antibody mutant may be substituted, generally with serine, to improve the oxidative stability of the molecule and to prevent aberrant cross-linking. Conversely, a cysteine may be added to the antibody to improve stability {particularly where the antibody is an antibody fragment, such as an Fv fragment). Another type of antibody mutant has an altered glycosylation pattern. That may be achieved by adding or deleting one or more carbohydrate moieties found in the antibody and/or by adding or deleting one or more glycosylation sites that are not present in the antibody. Glycosylation of antibodies is typically either N4inked to Asn or O-linked to Ser or Thr. The tripeptide sequences, asparagine-X-seiine and asparagine-X-threonine, where X is any arni.no acid except proline, are common recognition sequences for enzymatic attachment of a carbohydrate moiety to the asparagine side chain. N-acetylgalactosamine, galactose. fucose or xylose, for example, are bonded to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or S-hydroxylysine also may be used. Addition or substitution of one or more serine or threonine residues to the sequence of the original antibody can enhance the likelihood of O-linked glycosylation. It may be desirable to modify the antibody of the invention with respect to effector function, so as to enhance die effectiveness of the antibody, for example, cysteine residue(s) may be introduced in the .Ft region, thereby allowing interchain disulfide bond formation in that region. The homodimeric antibody thus generated may have improved internalization capability and/or increased cell killing mediated by complement and antibody-dependent cellular cytotoxicity (ADCC), see Caron et a,L J Exp Med 176:119.1 -1195 (1992) and Shopes, Immunol 148:2918-2922 (' 1993). Such an antibody derivative or analog also may be more resistant to degradation in vivo. Alternatively, an anced complement lysis and ADCC capabilities, see Stevenson et tibody can be engineered which has dual Fc regions and may thereby have enhanal., Anti-Cancer Drug Design 3: 219 230 (19S9). Covalent modifications of the antibody are included within the scope of the invention. Such may be made by chemical synthesis or by enzymatic or chemical cleavage of the antibody, if applicable. Other types of covalent modifications of the antibody are introduced into the molecule by reacting targeted amino acid residues of the antibody with an organic derivatizing agent that is capable of reacting with selected side chains or with the N-terminal or C-temuna! residue. Cysteinyl residues can be reacted with ot-haloacetates (and corresponding amines), such as chioroacetic acid or chloroacetamide, to yield carboxyimethy! 01 carboxyamidomethyl derivatives. Cysteinyl residues also can be derivatized by reaction with bromotriffuoroacetone, a-bromo-β(5-iimdo2oyl)prop.ionic acid, cbloroacetyl phosphate, N-alkylmaleimides, 3-nitro-2-pyridyl disulfide, methyl 2-pyridy.t disulfide, p-chloramercuribenzoate, 2-chloromercurar4-mtrophenol or chloro-7-nitrobertzo-2-oxa-l,3-diazole, for example. Histidyi residues can be derivatized by reaction with diethylpytocarbonate atpH 5.5-7.0. p-bromophenacyl bromide also can be used, the reaction is preferably performed in 0.1 M sodium cacodylate at pH 6.0. Lysinyl and a terminal residues can be reacted with succinic or other carboxylic acid anhydrides to reverse the charge of the residues. Other suitable reagents for derivatizing a-amino-containing residues include imidoesiers, such as, methyl picohnimidate, pyridoxal phosphate, pyridoxai, chloroborohydride. trinHrobeirzeuesulfonic acid, O-melhylisourea and 2,4-penlarieilione, and the amino acid can be transaminase-caialyzed with glyoxyiate. Arginyl residues can be modified by reaction with one or several conventional reagents, such as, phenylglyosaL 2,3-butanedione, ) ,2-cyclohexanediorte and ninhydrin. Derivatination of arginine residues often requires alkaline reaction conditions. Furthermore, the reagents may react with lysine as well as the arginine ε-amino group. The specific modification of tyrosyl residues can be made with aromatic diaxoriium compounds or tetranitromethane. For example, N-acetylimidizole and tetranitromethane are used to form O-aceiyl tyrosyl species and 3-nitro labeled proteins for use in a radioirmmomassay. respectively. Tyrosyl residues can be iodinated using ,2;F or L,ll to prep Carboxyl side groups (aspartyl or glutamyl) can be modified by reaction with carbodiimides ('R-N;C;:C-R'), where R and R' can be different alky! groups, Glutaminyl and asparaginyl residues are frequently deamidated to the corresponding glutamyl and aspartyl residues, respectively, under neutral or basic conditions. The deamidated form of those residues falls within the scope of this invention. Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of serinyl or threonyl residues, methylation of the «-amino groups of lysine, argmme, and histidine side chains (Creighton, Proteins; Structure and Molecular Properties, W.H. Freeman & Co., San Francisco, pp. 79-S6 (1983)), acetylaiion of the N terminal amine and amidation of any C terminal carboxyl group, Another type of covaient modification involves chemically or enzymatically coupling carbohydrates and glycosides to the antibody. Those procedures do not require production of the antibody in a host cell that has glycosylation capabilities for N-linked or O-linked glycosylation. Depending on the coupling mode vised, the sugar(s) may be attached to: (a) arginine and histidine; (b) free carboxyl groups; (c) free sulfhydryl groups, such as those of cysteine; (d) free hydroxyl groups, such as those of serine, threonine or hydroxy proline; (e) aromatic residnes such as those of phenylalanine, tyrosine or tryptophan; or (f) the amide group of ghuamine. Such methods are described in WO 87/05330 and in Apliu & Wrislon, CRC Grit Rev Biochem, pp. 259-306 (1981). Removal of any carbohydrate moieties present on the antibody may be accomplished chemically or enzymatically. Chemical deglycosylation. for example, can require exposure of the antibody to the compound, trill uoronietlmnesul tonic acid, or an equivalent compound, resulting in cleavage of most or all sugars except the linking sugar (N-acelylglucosamine or N-acecylgalactosamme), while leaving the antibody intact. Chemical deglycosylation is described, for example, in Haktmuddin et al., Arch Biochem Biophys 259:52 (1987) and in Edge et al., Anal Biochem 118:131 (1981). Enzymatic cleavage of carbohydrate moi eties on antibodies can be achieved by any of a variety of endoglycosidases and exoglycosidases as described, for example, in lliotakura et al., Meth Enzymoi 1.38:350(1987). Another type of covalem modification of the antibody comprises linking the antibody to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol or polyoxylalkyienes, in the manner set forth in U.S. Pat. Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,4.17; 4,791,192 or 4,179,337. Functional equivalents may be produced by interchanging different CDR's of different antibody chains within a framework, or a composite FR derived from plural antibodies. Thus, for example, different classes of antibody are possible for a given set of CDRs by substitution of different heavy chains, for example, IgGi-i, IgM, JgA-.2 or IgD, to yield differing extended Type I glycosphingoHpid antibody types and isotypes. Similarly, artificial antibodies within the scope of the invention may be produced by embedding a given set of ("PR's within an entirely synthetic framework. The antibody fragments and functional equivalents of the present invention encompass those molecules with a detectable degree of specific binding to extended Type I glycosphingoHpid. A detectable degree of binding includes all values in the range of at least 10-100%, preferably at least 50%, 60% or 70%, more preferably at least 75%, 80%, 85%, 90%, 95% or 99% of the binding ability of an antibody of interest. Also included are equivalents with an affinity greater than 100% that of an antibody of interest. The CDR/s generally are of importance for epitope recognition and antibody binding. However, changes may be made to residues that comprise the CDR/s without interfering with the ability of the antibody to recognize and to bind the cognate epitope. For example, changes that do not: impact epitope recognition, yet increase the binding affinity of the antibody for the epitope, may be made. Several studies have surveyed the effects of introducing one or more amino acid changes at various positions in the sequence of an antibody, based on the knowledge Thus, equivalents of an antibody of interest can be generated by changing the sequences of the heavy and light chain genes in the CDR1, CDR2 and/or CDR3, or in the framework regions, using methods such as obgonucleotide-mediated site-directed mutagenesis, cassette mutagenesis, error-prone PCR, DNA shuffling, amino acid modification or imitator-strains of E. coli (Vaughati et a!., 1998, Nat Biotech 16:535-539; and Adey el al, 1996, Chap. 16, pp. 277-291, in Phage Display of Peptides and Proteins, eds. Kay et al., Academic Press), for example. The methods of changing the nucleic acid sequence of the primary antibody can result in antibodies with improved affinity (Gram et at., 1992, Proc Natl Acad Set USA S9-.3576-35S0; Boder et al., 2000, Proc Natl Acad Set USA 97:30701-10705; Davies & Riechmann, 1996, hmmtnotech 2:169-179; Thompson et al., .1996, J Mol Biol 256:77-88; Short et al, 2002, J Bio! Chem 277:16365-16370; and Furakawa et al., 2001, i Biot Chem 276:27622-27628). Repeated cycles of "polypeptide selection" can be used to select for higher affinity binding by, for example, the selection of multiple amino acid changes which are selected by multiple selection of cycles. Following a first round of selection, involving a first region of selection of amino acids in the ligand or antibody polypeptide, additional rounds of selection in other regions or amino acids of die ligand are conducted. The cycles of selection are repeated until the desired affinity properties are achieved. Improved antibodies also include those antibodies having improved characteristics that are prepared by the standard techniques of animal immunization, hybridoma formation and selection for antibodies with specific characteristics. "Antagonist" refers to a molecule capable of inhibiting one or more biological activities associated with extended Type I gtycosphingolipid. Antagonists may interfere with the maintenance and the growth of a cell expensing a Type 1 glycosphingolipid. All points of intervention by an antagonist are considered equivalent for purposes of the instant invention. Thus, included within the scope of the invention are antagonists, e.g., neutralizing antibodies that bind to extended Type 1 glycosphingolipid. "Agonist1' refers to an antibody, an antibody fragment, a conjugate and so on, which activates one or more biological activities of extended Type I glycosphingolipid or a celt expressing same. Agonists can act as a mitogen of cells expressing a Type I glycosphingolipid. All pokus of intervention by art agonist shall be considered equivalent for purposes of the instant invention. Thus, included within the scope of the invention are antibodies that bind to extended Type 1 glycosphingolipid and enhance an activity, such as, differentiation, for example. The terms "cell," "cell line," and "cell culture" include progeny thereof. It is also understood that ail progeny may not be precisely identical such as, in DN A content, due to deliberate or inadvertent mutation. Variant progeny that have the same function or biological property of interest, as screened for in the original cell, are included in the scope of the invention. The "host cells" used in the present invention generally are prokaryotie or eukaryotic hosts, selected as a design choice. "Transformation" of a cellular organism, cell or cell line with a nucleic acid means introducing a nucleic acid into the target cell so that the nucleic acid is replicable, either as an extrachromosomal element or by chromosomal integration, and, optionally, expressed. "Transfecrion" of a cell or organism with a nucleic acid refers to the taking up of the nucleic acid, e.g., an expression vector, by the cell or organism whether or not any coding sequences are in fact expressed. The terms "transfected host cell" and "transformed" refer to a cell in which a nucleic acid was introduced. Typical prokaryotic host cells include various strains of E. coli. Typical eukaryotic host ceils are mammal cells, such as Chinese hamster ovary, or cells of human origin. The introduced nucleic acid sequence may be from the same species as the host cell or of a different species from the host cell, or may be a hybrid nucleic acid sequence, containing some foreign and some homologous nucleic acids, Transformation can also occur by transduction or infection with virus-derived elements or carriers. The term "vector" means a nucleic acid construct, a carrier, containing a nucleic acid, the ttansgene, the foreign gene or the gene of interest, which can be operably linked to suitable control sequences for expression of the transgene in a suitable host. Srtch control sequences include, for example, a promoter to effect transcription, an optional operator sequence to control such transcription, a sequence encoding suitable mRNA ribosome binding sites and sequences which control the termination of transcription and translation. The vector may be a plasmid, a phage particle or just a potential genomic insert. Once transformed into a suitable host, the vector may replicate and function independently of the host genome, or may in some instances, integrate into a host cell genome or odier nucleic acid. In the present specification, "plasmid" and "vector" are used interchangeably, as a plasmid is a commonly used form of vector. However, the invention is intended to include such other forms of vectors which serve equivalent carrier function as and which are, or become, known in the art, such as. viruses, phagemids. transposons, synthetic molecules that carry nucleic acids, liposomes and the like. "Mamma!" for purposes of treatment refers to any animal classified as a mammal, including human, domestic and farm animals, nouhuman primates, and zoo, sports or pet animals, such as dous, horses, cats, cows etc. The antibodies of interest can be screened or can be used in an assay as described herein or as known inilie art. Often, such assays require a reagent to be detectable, that is, for example, labeled. The word "label" when used herein refers to a detectable compound or composition which can be conjugated directly or indirectly to a molecule or protein, e.g., an antibody. The label may itself be detectable (e.g., radioisotope labels, particles or fluorescent labels) or may be an instrument to obtain a detectable signal, such as, in the case of an enzymatic label, may catalyze a chemical alteration of a substrate compound or composition which men is detectable. As used herein, "solid phase" means a matrix io which an entity or .molecule, such as, the antibody of the instant invention, can adhere or bind. Example of solid phases encompassed herein include Those formed partially or entirely of glass (e.g., controlled pore glass), polysaccharides (e.g., agarose), plastics, polypropylenes, polyacrylamides, polystyrene, polyvinyl alcohol and silicones. In certain embodiments, depending on the context, the solid phase can comprise the well of an assay plate; in others can be used in a purification column (e.g., an affinity chromatography column). Thus, the solid phase can be a paper, a bead, a plastic, a chip and so on, can be made from a variety of materials, such as nitrocellulose, agarose, polystyrene, polypropylene, silicon and so on, and can be in a variety of configurations. Cells expressing extended Type I glycosphingolipid or glycans thereof, such as celt membrane preparations, as well as purified extended Type 1 glycosphingolipid can be used as immunogens for generating antibodies of interest. The irmnnnogen can be obtained or isolated from natural sources or can be made synthesized enzymatically or chemically. Whole cells, such as extended Type I glycosphingolipid expressing ceils, cells derived from a natural source or from cancers, such as cancer cefl lines, can be used. Cells that overexpress extended Type 1 glycosphingolipid may be used as the iminunogen for making the antibodies of interest. Also, membrane preparations carrying extended Type .1 glycosphingolipid can he used, as known in the art. Such cells and portions thereof can be used as (he antigen source m a diagnostic assay. Nucleic acid molecules encoding amino acid sequence mutants can be prepared by a variety of methods known in die art. The methods include, but are not limited to. oligomicleotide-mediated (or site-directed) mutagenesis, PCR mutagenesis and cassette mutagenesis of an earlier prepared mutant or a non-mutant version of the molecule of interest, {see, for example, Kunkel, Proc Natl Acad Sci USA 82:488 (1985)). Recombinant expression of an antibody of the invention, or fragment, derivative or analog thereof, (e.g., a heavy or light chain of an antibody of (he invention, a single chain antibody of die invention or an antibody matein of the invention) includes construction of an expression vector containing a polynucleotide that encodes the antibody or a fragment of the antibody as described herein. Once a polynucleotide encoding an antibody molecule has been obtained, the vector for the production of the antibody may be produced by recombinant DNA technology as known in the art An expression vector is constructed containing antibody coding sequences and appropriate transcriptional and translations! control signals. The methods include, for example, in vitro recombinant DNA techniques, synthetic techniques and in vivo genetic recombination. The expression vector is transferred to a Sost. cell by conventional techniques and the tiansfected ceils then are cultured by conventional techniques to produce an antibody, or fragment, of the invention. ln one aspect of the invention, vectors encoding both the heavy and light chains may be co-expressed in the host A variety of bost/expression vector systems may be utilized to express the antibody molecules of the invention. Such expression systems represent vehicles by which the coding sequences of interest may be proceed and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleoside coding sequences, express an antibody molecule of the invention in situ. Bacterial cells, such as E. coli. and e-ukaryotic cells are commonly used for the expression of a recombinant antibody molecule. especially for the expression of whole recombinant antibody molecule.fot- example, mammal cells such as CHO cells, in conjunction with a vector, such as 0ne carrying the major intermediate early gene promoter element from humaay cytomegalovirus, are an effective expression system for antibodies {Foecking et all Gene 45:101 (1986); and Cockett et aL Bio/Technology B:2 (1990)). Plants ant plant cell culture, insect cells and so on also can be used to make (he proteins of interest, as known in (he art. In addition, a host cell is chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells can haw the particular characteristic and specific mechanisms for the desired post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen TO ensure the correct modification and processing of the expressed antibody of interest. Hence, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation and phosphorylation of the gene product may be used. Such mammalian host cells include, but are not limited to, CHO, COS, 293., 3T3 or myeloma cells. For long-term. high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the antibody-molecule may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DMA controlled by appropriate expression control elements (e.g., promoter, enhancer sequences, transcription terminators, poiyadenylation sites etc) and a selectable marker. Following the introduction of the foreign DNA. engineered cells may be allowed to grow for one to two days in an enriched media, and then are moved to a selective medium. The selectable marker in the recombinant plasmid confers resistance to the selection and allows celts to stably integrate the plasmid into a chromosome and be expanded into a cell line. Alternatively, an extrachromosoma! element can be maintained in the cells under selection. Such engineered cell lines not only are useful for antibody production but are useful in screening and evaluation of compounds that interact directly or indirectly with the antibody molecule. A number of selection systems may be used, including but not limited to using the Herpes simplex virus thymidine kinase (Wigler et al., Cell 11:223 (1977)), Ivypoxanthme-guaniue phospboribosyltransferase (Szybalska et al , Proc Nat! Acad Sci USA 48:202 (1992)), glutamate synthase, in the presence of methionine sulfoximide f'.Adv Drug Del J?ev 58, b71. 2006 and see the website or Vrtemtvie of Lonza Group Ltd.) and adenine phosphoribosy!transferase (Lowy et al., Cell 22:817 {1980)) genes in tk, hgprt or aprt celts, respectively. Also, antimetabolite resistance cars be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler etal, Proc Natl Acad Sci USA 77:357 (1980); O'Hare et al., Proc Natl Acad Sci USA 78:1527 (1981)); gpt, which confers resistance to mycophenolic acid (Mulligan et. al., Proc Natl Acad Sci USA 78:2072 (1981)); neo, which confers resistance to the aminoglycoside, G-41S (Wu et al., Biotherapy 3:87 (1991)); and hyg.ro, which confers resistance to hygromycin (Santerre et al.. Gene 30:147 {1984)). Methods known in the art of recombinant DMA technology may be routinely applied to select the desired recombinant clone, and such methods are described, for example, in Ausubel et al, eds., Current Protocols in Molecular Biology, John Wiley & Sons (1993); Kriegler, Gene Transfer and Expression, A Laboratory Manual. Stockton Press (1990); Dracopoii etal., eds., Current Protocols in. Human Genetics, John Wiley & Sons (1994); and Colberre-Garapm et al, 3 Mol Biol 150:1 (1981). The expression levels of an antibody molecule can be increased by vector amplification (for example, see Bebbingtonet at., in DNA Cloniny, Vol 3. Academic- Press (i 987)). When a marker in the vector system expressing antibody is amplifiable, an increase in the level of inhibitor present in the culture will increase the number of copies of the marker gene, Since the amplified region is associated with the antibody gene, production of the antibody will also increase (Crouse et al., Mol Cell Bio! 3:257 (.1983)). The host cell may be co-transfected with two or more expression vectors of the invention, for example, the first vector encoding a heavy chain-derived polypeptide and the second vector encoding a light chain-derived polypeptide. The. two vector's may contain identical selectable markers which enable equal expression of heavy and light chain polypeptides. Alternatively, a single vector may be used which encodes, and is capable of expressing, both heavy and light chain polypeptides. In such situations, the light chain can be placed before the heavy chain to avoid an excess of toxic free heavy chain (Prondfoot, Nature 322:52 (1986); and Kohler, Proc Natl Acad Sci USA 77:2197 (1980)). The coding sequences for the heavy and light chains may comprise cDNA or genomic DNA. Once an antibody molecule of die invention has been produced by an animal, chemically synthesized or reconibinantly expressed, it may be purified by any method known in the art for purification of an immunoglobulin molecule, for example, by chromatography (e.g., ion exchange, affinity, particularly by affinity for extended Type I glycosphingolipid after Protein A and size-exclusion chromatography, and so on), centrifugation, differential solubility or by any other standard technique for the purification of proteins. In addition, the antibodies of the instant invention or fragments thereof can be fused to heterologous polypeptide sequences described herein or otherwise known in the art, to facilitate purification. The antibodies of the present invention may be generated by any suitable method known in the art. Thus, a purified extended Type I structure can be used as antigen, optionally, with an adjuvant, snch as, complete or incomplete Freirad's adjuvant. The antibodies of the present invention may comprise polyclonal antibodies, although because of the modification of antibodies to optimize use in human, as well as to optimize the use of the antibody per se, monoclonal antibodies are preferred because of ease of production and manipulation of particular proteins. Methods of preparing polyclonal antibodies are known to the skilled artisan (Harlow et at., Antibodies: a Laboratory Manual, Cold Spring Harbor Laboratory Press, 2nd ed.(l988)). For example, an immunogen, as exemplified herein, may be administered to various host animals including, but not limited to, rabbits, mice, camelids, rats etc., to induce the production of serum containing polyclonal antibodies specific for extended Type I glycosphingolipid. The administration of the immunogen may entail one or more injections of an immunizing agent and. if desired, an adjuvant. Various adjuvants maybe used to increase the immunological response, depending on the host species, and include, but are not limited to, Freund's (complete and incomplete), mineral oil, gels, alum (aluminum hydroxide), surface active substances, such as tysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, keyhole limpet hemocyanins (KLB), dinitrophenol and potentially useful human adjuvants, such as BCG (bacille CalmeWe-Guerin) and Corynebacterium parvum. Additional examples of adjuvants which may be employed include the MPL-TDM adjuvant (monophosphoryl lipid A, synthetic trehalose dicorynomycolate). Imthat elicit an immune response in the animal host chosen. Thus, various administratiomunization protocols are well known in the art and may be performed by any method n routes can be used over various time periods as a design choice. Typically, the immunogen (with or without adjuvant) is injected into the mammal by multiple subcutaneous or intraperitoneal injections, or intramuscularly or intravenously, in certain circumstances, whole cells expressing extended Type I glycosphingoiipid can be used. Depending on the nature of the immunogen (i.e., percent hydrophohi city, percent, hydrophilicity, stability, net charge, isoelectric point etc.), the extended Type I glycosphingoiipid or portion thereof may be modified or conjugated to be immunogenic or more immunogenic in the animal, such as a mammal, being immunized. For example, extended Type 1 glycosphingoiipid or a portion thereof can be conjugated to a carrier. The conjugation includes either chemical conjugation by derivatizing active chemical functional groups on either or both the immunogen and the immunogenic protein to be conjugated such that, a covalent bond is formed or other methods known to the skilled artisan. Examples of such carriers or immunogenic proteins include, but are not limited to, K.LH, ovalbumin, serum albumin, bovine thyroglobulin, soybean trypsin inhibitor and promiscuous T helper peptides. Various adjuvants may be used to increase the immunological response as described above. Once a suitable preparation is obtained, it is possible to isolate particular antibodies from the plural antibodies by known separation techniques- such as affinity chromatography, panning, absorption and so on. in that way, an individual antibody species can be obtained for further study, for example, sequencing to obtain the amino acid sequences of one or more CD lis. The antibodies of the present invention preferably comprise monoclonal antibodies- Monoclonal antibodies may be prepared using hyh.ridoma. technology. such as described by Kohler et al.. Nature 256:495 (1975); U.S. Pat. No. 4 J76.110; Harlow et ah, Antibodies: A laboratory Manual, Coid Spring J [arbor Laboratory Press, 2nd ed. (1988); and Hammerling et al, Monoclonal Antibodies and T-Cell Hybridomas, Elsevier (1981), recombinant DNA methods, for example, making and using transfectomas, or other methods known to the artisan. Other examples of methods which may be employed for producing monoclonal antibodies include, but are not limited to, the human B-cell hybridoma technique (Kosbor et ah, immunology Today 4:72 (1983); and Cole etal., Proc Natl Acad Sci USA 80:2026 (1983)), and the EBV-hybridoma technique (Cole etal. Monoclonal Antibodies and Cancer Therapy, pp. 77-96. Alan R. Liss (1985)). Such antibodies may be of any immunoglobulin class including IgG, IgM, lgB, IgA and IgD, and any subclass thereof. The hybridoma producing the mAb of the invention may be cultivated in vitro or in vivo. In the hybridoma model, a host such as a mouse, a humanized mouse, a transgenic mouse with human immune system genes, horse, sheep, hamster, rabbit, rat, camel or any other appropriate host animal is immunized to elicit lymphocytes that produce or are capable of producing antibodies that specifically bind to extended Type I glycosphingolipid. Alternatively, lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Coding. Monoclonal Antibodies: Principles and Practice, Academic Press, pp. 59-103 (1986)). Generally, in making antibody-producing hybridomas, either peripheral blood lymphocytes ("PBLs") arc used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine or human origin. Typically, a rat or mouse myeloma cell line is employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized ceils. For example, if the parental cells lack the enzyme, hypoxnmhine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin and thymidine ("HAT medium"), substances that prevent the growth of HGPRT-deficient cells. Preferred immortalized cell lines are those that fuse efficiently, support stable high level production of antibody by the selected antibody-producing cells, and are sensitive to a medium, such as HAT medium. Among die myeloma cell lines are murine myeloma lines5 such as those derived from the MOPC-21 and MPC-ll mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, Calif, and SP2/0, 'FO or X63-Ag8-653 cells available from the American Type Culture Collection, Manassas. VA. The mouse myeloma cell line NSO also may be used (European Collection of Cell Cultures, Salisbury, Wilsture, UK). Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J fmmunof tS3:300i (1984)\ and"Brodeur et at, monoc/onai Antibody Production Techniques ?tnd Applications, Marcel Dekfcer, lite, pp, 51-63 (1987)). Another alternative is to use electrical fusion rather titan chemical fusion to form hybridomas. Instead of chemical fusion, a B tell can be immortalized using, for example, Epstein Barr Virus or another transforming gene, see, e.g., Zurawaki et a.L, in Monoclonal Antibodies, ed., Kennett et aL Plenum Press, pp. 19-33. (1980). Transgenic mice expressing immunoglobulins and severe combined immvinocleficient (SOD) mice transplanted with human B lymphocytes also can be used. The culture medium in which hybiidoma cells are grown is assayed for production of monoclonal antibodies directed against extended Type 1 glycosphingolipid. The binding specificity of monoclonal antibodies produced by hybridoma cells may be determined by immunoprecipiiation or by an in vitro binding assay, such as radioimmunoassay (R1A), fhiorocytometric analysis (FACS) or enzyme-1 inked immunosorbent assay (BL1SA). Such techniques are known in the art and are within the skill of the artisan. Also, the Biacore system can be used, as known in the art. The binding affinity of the monoclonal antibody to extended Type [ glycosphmgolipid can, for example, be determined by a Scatchard analysis (Munson et. at., Anal Biochem 307:220(1980)). After hybridoma cells that produce antibodies of the desired specificity, affinity and/or activity are identified, the clones may be subcloned by limiting dilution procedures arid grown by standard methods (Coding, Monoclonal Antibodies: Principles and Practice, Academic Press, pp. 59-103 (1986)), Suitable culture medium includes, for example, Dulbecco's Modified Eagle's Medium (D-MEM) or RPMI-1640. hi addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal. The monoclonal antibodies secreted by the subclones are suitably separated or isolated from the culture medium, ascites fluid or serum by conventional immunoglobulin purification procedures such as, for example, protein A Sepharose, protein G Sepharose, hydroxylapatite chromatography, gel exclusion chromatography, ge! electrophoresis, dialysis or affinity chromatography. A variety of methods exist in the art for the production of monoclonal antibodies and dius, the invention is not limited to their sole production in hybridomas. For example, the monoclonal antibodies maybe made by recombinant DMA methods, such as those described in U.S. Pat. No. 4,816,567. Alternatively, human antibodies can be obtained from transgenic animals, such as the KM mouse, discussed above. In that context, the term "monoclonal antibody" refers to an antibody derived from a single enkaryotic, viral or prokaryotic clone. Thus, using human cancer cells known to express an extended Type \ chain structure, such as Colo205 cells, or an extended Type I chain containing compound, such as glycosphingolipid, such as Le',T,e'\ as antigen, inbred or transgenic mice ave immunized and boosted as known in the art. Spleens were obtained, cells fused to myeloma cells and hybridomas made and miltired. Cell supemalants were screened by KL1SA using, for example. Leb/Le* as the capture reagent. Positive clones were amplified. IMH2 is an example of a mouse l3G3 monoclonal antibody that binds specifically to an extended Type I chain structure. Using a transgenic mouse model, human antibodies can be produced by immunizing the transgenic mice with a extended Type I chain immunogen. Such antibodies can be generated on a fee basis, for example, by Medarex, NJ and Amgen. CA. Using the KM mouse, the GNX-8 (IgGj) monoclonal antibody was selected for further characterization and use. GNX-8 is a cytotoxic antibody. In assays using Coio205 colon cancer cells as targets, GNX-8 lysed the cancer cell line cells; and at least at 50 ug/ml the antibody lysed all cells in the culture. GNX-8 does not bind to RBCs. The antibody binds to colorectal cancer cells, breast cancer cells and lung cancer cells. Unlike IMH2, GNX-8 does not bind to Ley-Lex or Ley. DMA encoding the monoclonal antibodies of the invention is readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies, or such chains from human, humanized or other sources) (Innis et al. in PCR Protocols. A Guide to Methods and Applications, Academic (1990) and Sanger et al., Proc Nat! Acad Sci 74:5463 (1977)). The hybridoma cells can serve as the source of such DNA. Once isolated, the DMA may be placed into expression vectors, which are then transacted into host, cells such as H. c-oli cells, NSO cells, COS cells, Chinese hamster ovary (CHO) cells or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also may be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Pal. No. 4,816,567; and Morrison et at., Proc Nail Acad Sci USA 81:6851 (1984)) or by covakntly joining to the immunoglobulin coding sequence, al! or part of the coding sequence of a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one extended Type i glycosphingohpid-combining site of an antibody of the invention to create a chimeric bivalent antibody. The antibodies may be monovalent antibodies. Methods for preparing monovalent antibodies are weli known in the art. For example, one method involves recombinant expression of immunoglobulin light chain and modified heavy chain. The heavy chain is truncated generally at any point in the Fc. region so as to prevent heavy chain cross-linking. Alternatively, the relevant cysteine residues are substituted with another amino acid residue or are deleted so as to prevent cross-linking. Antibody fragments which recognize specific epitopes may be generated by known techniques. Traditionally, those fragments are derived via proteolytic digestion of intact antibodies (see, e.g., Morimoto et al, J Biochem Biophys Methods 24:107 (1992); and Brerman et al, Science 229:81 (i 985)}. Por example, Fab and 1W): fragments of the invention may be produced by proteolytic cleavage of immunoglobulin molecules, using enzymes, such as, papain (to produce Fab fragments) or pepsin (to produce F(nb)2 fragments). F(ab)2 fragments contain the Variable region, the light chain constant region and the CH1 domain of the heavy-chain. However, those fragments can be produced directly by recombinant host cells. For example, the antibody fragments can be isolated from an antibody phage library. Alternatively, F(nb)2-SH" fragments can be directly recovered from E. coli and chemically coupled to form F(ab)2 fragments (Carter et al., Bio/Technology 10:163 (1992). According to another approach, F(ab')2 fragments' can be isolated directly from recombinant host cell culture. Other techniques for the production of antibody fragments will be apparent to the skilled practitioner. In other embodiments, the antibody of choice is a single chain Fv fragment (Fv), see, for example, WO 93/16185. For some uses, including in vivo use of antibodies in humans and in vino detection assays, it may be preferable to "use chimeric, humanized or human antibodies. Methods for producing chimeric antibodies are known in the art, see e.g., Morrison, Science 229.1202 (1985); Oi et al., BioTechniques 4:214 (1986); Gillies et aL, J Immunol Methods 125:191 (1989); and U.S. Pat. Nos. 5,807,715; 4,816,567; and 4,816397. Humanized antibodies are derived from antibody molecules generated in a non-hmnan species that bind extended Type I glycosphingolipid wherein one or more CDR'?s therefrom are inserted into the FR regions from a human immunoglobulin molecule. Antibodies can be humanized using a variety of techniques known in the an including, for example, CDR grafting (EPO 239,400; WO 91/09967; and U.S. Pat. Nos. 5,225,539: 5,530,101; and 5,585,089), veneering or resurfacing (EPO 592,106; EPO 519,596; Padlan, Molecular Immunology 28:489 (1991); Studnicka eta!., Protein Engineering7:805 (1994); andRoguska etal.,Proc Natl Acad Sci USA 91:969 (1.994)), and chain shuffling (U.S. Pat. No. 5,565332). A humanized antibody has one or more amino acid residues from a source that is non-human. The non-human amino acid residues are often referred io as "import" residues, which are typically taken from an "import" variable domain. Humanization can be essentially performed following the methods of Winter et aL (Jones et aL Nature 321:522 (1986); Riechmann et aL Nature 332:323 (1988); and Vethoeyen et aL Science 239:1534 (1988)), by substituting non-human CDR's or portions of CDR sequences for the corresponding sequences of a human antibody. Accordingly, such "humanized" antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possible some FR residues are substituted from analogous sites in rodent antibodies. The heavy chain constant region and hinge region can be from any class or subclass to obtain a desired effect, such as a particular effector function. Often, framework residues in the human framework regions can be substituted with the corresponding residue from the CDR donor antibody to alter, and possibly improve, antigen binding. The framework substitutions are identified by methods known in the art, e.g., by modeling of the interactions of the CDR and framework" residues to identify framework residues important for antigen binding and sequence comparison to identify unusual framework residues at particular positions, see, e.g., U.S. Pat. No. 5,585,089; and Riechmann et ai., Nature 332:323 (1988). It is further preferable that humanized antibodies retain high affinity for extended Type I giycosphingolipid, and retain or acquire other favorable biological properties. Thus, humanized antibodies can be prepared by a process by analyzing the parental sequences and various conceptual humanized antibody derivatives using three-dimensional models of the parental and humanized sequences. The hypothetical three-dimenstonal immunoglobulin models are commonly available and are familiar to those skilled in the art. Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of the displays permits analysis of the likely role of certain residues in the functioning of die candidate immunoglobulin sequence, i.e., the analysis of residues that influence die ability of the candidate immunoglobulin to bind extended Type I giycosphingolipid. In that way, FK residues can be selected and combined from the recipient and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigen, is maximized, although it is the CDR residues that directly and most substantially influence extended Type 1! giycosphingolipid binding. The CDR regions also can be modified to contain one or more amino acids that vary from that obtained from the parent antibody from which the CDR was obtained, to provide enhanced or different properties of interest, such as binding of greater affinity or greater avidity, for example. Certain portions of the constant regions of antibody can be manipulated and changed to provide antibody homologs, derivatives, fragments and the like with properties different from or better than that observed in the parent antibody. Tims, for example, many lgG4 antibodies form imrachain disulfide bonds near the hinge region. The intrachain bond can destabilize the parent bivalent molecule forming monovalent molecules comprising a heavy chain with the associated light chain. Such molecules can reassociate, but, on a random basts. Another set of amino acids suitable for modification include amino acids in the area of the hmge which impact antibody functions, such as, binding of a molecule containing a heavy chain with binding to the Fc receptor and internalization of bound antibody. Such amino acids include, in l«Gl molecules, residues from about 233 to about 237 (Glu-Leu-Leu-Gly-Gly, SEQ ID NOT); from about 252 to about 256 (Met-lle-Ser-Arg-Thr, SEQ ID NO:2) and from about 318 (Glu) to about 331 (Pro), including, for example, Lysi^, Lys JX>. and Pro?,^. Completely hitman antibodies are particularly desirable for therapeutic treatment of human patients. Human antibodies can lie made by a variety of methods known in the art including phage display methods described above using antibody libraries derived from human immunoglobulin sequences, see, U.S. Pat. Nos. 4.444,887 and 4,716,111; and WO 98/46645, WO 98/50433, WO 98/24893, WO 98/16654", WO 96/34096, WO 96/33735 and WO 91/10741. The techniques of Cole et al. and Boerder et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss (1985); and Boerner et al, J Immunol 147:86 (1991)). Human antibodies can also be produced using transgenic mice which are incapable of expressing functional endogenous immunoglobulins, but which also express certain human immunoglobulin genes. For example, the human heavy and light chain immunoglobulin gene complexes may be introduced randomly or by homologous recombination into mouse embryonic stem cells. Alternatively, the human variable region, constant region and diversity region may be introduced into mouse, embtyowk stem cells, in addition y> the 5\vwvww heavy and light ch«i« genes. The mouse heavy and tight chain immunoglobulin genes may be treated so us to be non-functional separately or simultaneously with die introduction of the human immunoglobulin loci by homologous recombination. In particular, homozygous deletion of the JH region prevents endogenous antibody production. The modified embryonic stem cells are expanded and mieroinjected into blastocysts to produce chimeric mice. The chimeric mice are then bred to produce homozygous offspring which express human antibodies, see, e.g., Jakobovids et al., Proc Nail Acad Sci USA 90:255.1 (1993); Jakobovitis et al., Nature 362:255 (1993); Bruggermann et al., Year in Immunol 7:33 (1993); and Duchosal et al., Nature 355:258 (1992)). The transgenic mice are immunized in the normal fashion with an extended Type I glycosphingolipld, e.g., all or a portion of extended Type I glycosphingolipid, or a membrane preparation containing same. Monoclonal antibodies directed against extended Type 1 glycosphingolipid can be obtained from the immunized, transgenic mice using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation. Thus, using such a technique, it is possible to produce therapeutically useful igG, IgA, IgM and IgE antibodies. For an overview, see Lonberg et al, Int Rev Immunol 13:65-93 (1995). For a discussion of producing human antibodies and human monoclonal antibodies and protocols for producing such antibodies, see, e.g., WO 98/24893; WO 92/01047; WO 96/34096; and WO 96/33735; EPONo. 0 598 877; and U.S. Pat. Nos. 5,413,923; 5,625,126; 5,633,425; 5,569,825; 5,661,0.16; 5,545,806; 5,814,318; 5,885,793; 5,916,773; and 5,939,598. In addition, companies such as Amgen (Fremont, CA), Genpharm ($an Jose, CA) and Medatex, Inc. (Princeton, NJ) can be engaged to provide human antibodies directed against extended Type I giycosphingolipid using technology similar to that described above. Also, human mAbs could be made by immunizing mice transplanted with human peripheral blood leukocytes, splenocytes or bone marrow (e.g., trioma technique of .XTL Biophaimaceuticals, Israel). Completely human antibodies which recognize a selected epitope can be generaied using a technique referred to as "guided Selection." hi that approach, a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope (Jespers et al., Bio/Technology 12:899 (1988)). When using recombinant techniques, the antibody variant can be produced intracellularly, in the periplastic space, or directly secreted into the medium. If the antibody variant is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, may be removed, for example, by centrifugation or ultrafiltration. Carter et al, Bio/Technology 10:163 (1992) describe a procedure for isolating antibodies which are secreted to the peripiasmic space of E. colii. Briefly, cell paste is exposed to sodium acetate (pH 3.5} and EDTA. Cell debris can be removed by centrifugal ion. Where the antibody variant is secreted into the medium, supernatant from sue!) expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit. A protease inhibitor, such as, PMSF, may be included to inhibit proteolysis, and antibiotics may be included to prevent growth of adventitious contaminants. The antibody composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis and affinity chromatography. The suitability of protein A or protein G as an affinity ligand depends on the species and isotype of an immunoglobulin Ft domain that is present in the antibody variant. Protein A can be used to purify antibodies that are based on human IgG 1, lgG2 or IgG4 heavy chains (Lindmark et al., J Immunol Meth 62; 1 (1983)). Protein G can be used for mouse isotypes and for human IgG3 (Guss et al., EMBO J 5:1567 (1986)), The matrix to which the affinity ligand is attached is most often agarose, but other matrices are available. Mechanically stable matrices, such as controlled pore glass or poly(styrenedivinyl)benzene, allow for faster flow rates and shorter processing times than can be achieved with agarose. Where the antibody variant comprises a Cm domain, the Bakerbond ABXTM resin (JT Baker; Phillipsburg, NJ) is useful for purification. Other techniques for protein purification, such as, fractionation on an ion-exchange column, ethanol precipitation, reverse phase HPLC, chromatography on silica, chromatography on heparin agarose chromatography on an anion or cation exchange resin (such as a polyaspartic acid column), chromatofocusing, SDS-PAGE and ammonium sulfate precipitation are also available, depending on the antibody or variani to be recovered. Following any preliminary purification step(s), the mixture comprising the antibody or variant of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pli of between about 2.5-4.5. preferably performed at low salt concentrations (e.g., from about 0-0.25 M salt). Further, antibodies of the invention can, in turn, be utilized to generate anti-idiotype antibodies that "mimic' extended Type I giycosphingoiipid using techniques well known to those skilled in the art (see, e.g., Greenspan et aL F'ASEB J 7:437 (1989); and Nissinoff J Immunol 147:2429 (1991)). For example, antibodies which bind to and competitively inhibit muliimerization. and/or binding of a ligand to extended Type I giycosphingoiipid can be used to generate anti-idiotypes thai "mimic" extended Type I giycosphingoiipid. Such neutralizing anti-idiotypes or Fat, fragments of such anti-idiotypes can be used in therapeutic or diagnostic regimens. The antibodies of the present invention maybe bispecific antibodies. Bispecific antibodies can be monoclonal, preferably huttian or humanized, antibodies that have binding specificities for at least two different antigens. In the present invention, one of the binding specificities is directed towards extended Type 1 giycosphingoiipid, whereas the other specificity .may be for any other antigen, such as a cell-surface protein, receptor, receptor subunit, ligand, tissue-specific antigen, viral, protein, vitally-encoded envelope protein, pharmacologically active agent, such as a drug, hactefially-derived protein, bacteria! surface protein etc. Methods for making bispecific antibodies are well known. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin Heavy ehairvligrti chain pairs, where the swo heavy chains have different specificities (Mitstein et al. Nature 305:53? (1983)). Because of the random assortment of immunoglobulin heavy and light chains, the hybridomas (quadromas) produce a potential mixture of about ten different antibody molecules, of which only about one might have the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829 and in Traunecker et al., E'MRO J 10:3655 (1991). Other methods for making hispedfic antibodies are provided in, for example, Kufer et al., Trends Biotech 22.238-244, 2004. Antibody variable domains with the desired binding specificities can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an inmiunoglobuim heavy chain constant domain, comprising at least part of the hinge, CHI and Cm regions. It may have the first heavy chain constant region (CHI.) containing the site necessary for light chain binding present in at least one of the fusions. DNA's encoding the immunoglobulin heavy chain fusions and, if desired t the immunoglobulin light chain, arc inserted into separate expression vectors, and are co-transformed into a suitable host organism. For further details of generating bispecific antibodies see, for example Suresh et al., Meth Enzym 123:2I0 (1986). Heteroconjugate antibodies are also contemplated by the present invention. Heteroconjugate antibodies are composed, of two covakntly joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Pat. No. 4,676,930). It is contemplated that the antibodies may be prepared in vitro using known methods in synthetic protein chemistry, including those involving cross-linking agents. For example, immunotoxms may be constructed using a disulfide exchange reaction or by forming a thioester bond. Examples of suitable reagents for that purpose include iminothiolate and methyl-4-mercaptobutyrimidat.e, and those disclosed, for example, in U.S. Pat. No. 4,676,980. in addition, one can generate single domain antibodies fo extended Type I glycosphmgolipid. Examples of that technology have been described in W09425591 for antibodies derived from Camelidae heavy chain !g, as well as in US20030130496 describing die isolation of single domain fully human antibodies from phage libraries. Alternatively, techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946778; Bird, Science 242:423 (I9S8); Huston et al., Proc Natl Acad Sci USA 85:5879 (.1988); and Ward et al., Nature 334:544 (I9S9)) can be practiced. Single chain antibodies are formed by linking the heavy and tight chain fragments of the Fv region via an amino acid bridge, resulting in a single chain polypeptide. Techniques for the assembly of functional Fv fragments in E. coli may also be used (Skerra et. al., Science 242:1038 (1988))- Single chain antibodies ("scFv") and a method of their construction are described in, for example. U.S. Pat No. 4,946,778. Alternatively, Fab can be constructed and expressed by similar means. All of the wholly and partially human antibodies can be less immunogenic than wholly murine mAbs, and the fragments and single chain antibodies also can be less immunogenic. The instant invention encompasses antibodies recombiruuuly fused or chemically conjugated (including both covalentiy and non-covalently conjugations) to a polypeptide. Fused or conjugated antibodies of the present invention may be used for ease in purification, see e.g., WO 93/21232; EP 439,095; Naramura et al, Immunol Lett 39:91 (1994); U.S. Pat. No. 5,474,981; Gillies et al., Proc Natl Acad Sci USA 89:1428 (1992); and Fell etal., J Immunol 146:2446 (1991). The purification can be facilitated by using a recognition marker or tag. For example, the marker can be an amino acid sequence, such as, a hexa-hisiidine peptide, such as the tag provided in apQE vector (Qiagen, inc.. Cbatsworth, CA). among others, many of which are commercially available, Geutz et al., Proc Natl Acad Sci USA 86:821 (1989). Other peptide tags useful for purification include, but are not limited to, the "HA" tag. which corresponds to an epitope derived from the influenza hemagglutinin protein (Wilson et al., Cell 37.767 (1984)) and the "flag" tag. Antibodies or antibody fragments can be isolated from antibody phage libraries generated using the techniques described in McCafferty et al., Nature 348:552 (1990). Ciarkson et al. Nature 352:624(1991) and Marks et al., J Mol Biol 222:58 i (1 991) describe the isolation of murine and human antibodies, respectively, using phage libraries. Subsequent publications describe the production of high affinity (nM range) human antibodies by chain shuffling (Marks et a!., Bio/Technology 10:779 (1992)), as well as combinatorial infection and in vivo recombination as a strategy for constructing very targe phage libraries (Waterhouse et al., Nucl Acids Res 21:2265 {1993)). Thus, the techniques are viable alternatives to traditional monoclonal antibody hybridoma techniques for isolation of monoclonal antibodies. Candidate anti-extended Type I glycosphingolipid antibodies can be tested by enzyme-linked immunosorbent assay (ELLS A), FAC'S, Western immunobiotting or otlter immunochemical techniques, as known in the art. Tints, B cells or cells expressing extended Type I glycosphingolipid can be used to detect antibody binding thereto using a known technique, or suitable membrane preparations containing extended Type 3 glycosphingolipid or portion thereof or purified or isolated extended Type 1 chain structures can be adhered to a solid phase and used as a capture element in an assay, configured as a design choice. To determine whether a particular antibody homolog binds to human extended Type I glycosphingolipid, any conventional binding assay may be used. Useful extended Type 1 glycosphingolipid binding assays include FACS analysis, HLISA assays, radioimmunoassays and the like, which detect binding of antibody, and functions resulting therefrom, to human extended Type I giycosphiugoiipid. Full-length and soluble forms of human extended Type I glycosphingolipid taught herein are useful in such assays. The binding of an antibody or homolog to extended Type I glycosphingolipid, or to soluble fragments thereof, may conveniently be detected through the use of a second antibody specific for immunoglobulins of the species from which the antibody or homolog is derived. The second antibody can carry a delectable label or configured to be detected. 'Hie ability of an antibody or homolog to bind to human extended Type I glycosphingolipid can be evaluated by testing the ability thereof to bind, to human extended Type .1 glycosphingolipid' cells. Suitable extended Type I glycosphingolipid' cells for use in determining whether a particular antibody or homolog binds to human extended Type 1 glycosphingolipid are available mammal tissue culture cells expressing extended Type I glycosphingolipid, such as, on the cell surface. Binding of the antibody or homolog to the extended Type I glycosplungolipid* cell can be detected by staining the cells with, for example, a fjuorescently-labeled second antibody specific for immunoglobulins of die same species from which the antibody homolog being tested is derived. A fluorescence activated cell sorter ("FACS") can be used to detect and to quantify any binding, see generally, Shapiro, Practical Flow Cytometry, Alan R. Liss. inc.. New York, N.Y. (1985). To determine whether a particular antibody or homolog causes no significant decrease in the number of circulating extended Type [ giycosphingoiipid1 cells in vivo, the number of circulating extended Type i glycosphingolipid: cells isolated from a mammal within 24 hours after administration of the antibody or homolog to a mammal having normal immune function is quantified, and compared to the pre-administration number or the number in a control mammal to whom an isotypc -matched antibody or homolog of irrelevant specificity' has been administered instead of an antibody or homolog of the instant invention. Quantification of extended Type I giycosphingolipid" cells in animals dosed with an extended Type I glycosphingolipki antibody or functional portion or derivative thereof may be accomplished, for example, by staining obtained cells with fluorescently-labeled antibodies that bind the anti-extended Type I glycosphingolipid antibodies, as well as labeled antibodies specific for T cells and 8 cells, followed by FACS analysis. Antibodies of the instant invention may be described or specified in terms of the epitope(s) or portion(s) of extended Type 1 glycosphingolipid to which the antibody recognizes or specifically binds. The epitope(s) may be specified as described herein, e.g.. by physical means, such as mass spectrometry, compositional analysis of the saccharides, the molecules to which the sugars bind, conformational epitopes and so on. Antibodies of the -instant invention may also be described or specified in terms of cross-reactivity. Antibodies that bind extended Type I glyeosphingolipids, which have at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least. 70%s at least 65%, at least 60%, at least 55%. and at. least 50% identity {as calculated using methods known in the art and described herein) to extended Type [ glycosphingolipid are also included in die instant invention. Antibodies of the instant invention also may be described or specified in terms of binding affinity to an extended Type I glycosphingolipid of interest. Anti-extended Type I glycosphingolipid antibodies may bind with a K1» of less than about 10"7 M, less than about I0-6 M, or less than about 10"; M. Higher binding affinities in an antibody of interest can he beneficial, such as those with an equilibrium dissociation constant or KD of from about 10-8 to about 10-15 M or more, from about 10"s to about 10-12 M, from about 10' to about 10-11 M, or from about lO-81 10 about 10-10 M. The invention also provides antibodies that competitively inhibit binding of an antibody to an epitope of the invention as determined by any method known in the art for determining competitive binding, for example, the immunoassays described herein. In preferred embodiments, the antibody competitively inhibits binding to the epitope by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 70%, at least. 60%, or at least 50%. The instant invention also includes conjugates comprising an antibody of interest. The conjugates comprise two primary components, an antibody of interest and a second component, which may be a cell-binding agent, a cytotoxic agent, a pharmacologically active, agent, a drug and so on. As used herein, the term "cell-binding agent" refers to an agent that specifically recognizes and binds to a molecule on the cell surface. Thus, the cell-binding agent can be one that binds a CD antigen, a pathogen antigen, such as a vims antigen, a differentiation antigen, a cancer antigen, a cell-specs tic antigen, a tissue-specific antigen, an l.g or Ig-likc molecule and so on. Cell-binding agents may be of any type as presently known, or that become known, and includes peptides, non-peprides, saccharides, nucleic acids, iigands, receptors and so on, or combinations thereof. The cell-binding agent may be any compound that can bind a cell, either in a specific or non-specific manner. Generally, the agent can be an antibody (especially monoclonal antibodies), lymphokines, hormones, growth factors, vitamins, nutnent-lransport molecules (such as transferrin), or any other cell-binding molecufe or substance. Other examples of cell-binding agents thatch be used include: polyclonal antibodies; monoclonal antibodies; and fragments of antibodies such as Fab„ Fab, FfBK)2 and Fv fragments (Paham, J. Immunol. 131:2895-2902 (1983); Spring et aL, J. Immunol. 1.13:470-478 (1974); and Nisonoff el aL Axch. Biochem. Biophys. 89: 230-244 (I960)). The second component also can be a cytotoxic agent. The term "cytotoxic agent" as used herein refers to a substance that reduces or blocks the function or growth, of ceils and/or causes destruction of cells. Thus, the cytotoxic agent can be a taxol, a maytansinoid, such as, DM1 or DM4, C01065 or a CO 1065 analog, a ricin, a drug, mitomycin C and so on. In sorue embodiments, the cytotoxic agent, as with any binding agent of a conjugate of the mstaut invention, is covaSently attached, directly or viaa ckavabk or non-ckavabk linker, to an ant'teooy of interest. Examples of suitable maytansmoids include maytansinol and maytansinol analogs. Maytansinoids inhibit microtubule formation and are highly toxic to mammalian celts. Examples of suitable maytansinol analogues include those having a modified aromatic ring and those having modifications at other positions. Such suitable maytansinoids are disclosed in U.S. Patent Nos. 4,424.219; 4.256,746; 4,294,757; 4,307,016; 4,313,946; 4,315,929: 4,331,598; 4,361,650; 4,362,663; 4,364,866; 4,450,254,4.322,348; 4,371,533; 6,333,410; 5,475,092; 5,585,499; and 5,846,545. Examples of suitable analogues of having a modified aromatic ring include: (I) C-19-decbloio (U.S. Pat. ImaYtansmolSO. 4,256,746) (prepared, for example, by LAH reduction of ansamytocin P2); (2) C-20-hydroxy (or 020-demetbyl)+1--19-Cdechioro (U.S. Pat. Nos. 4,36.1 ,650 and 4,307,016) (prepared, for example, by demethylation using Streplomyces or Actinomyces or dechlorination using lithium aluminum hydride (LAH)); and (3) C-20-demethoxy. Examples of suitable analogues of maytansinoi having modifications of other positions include: (J) C-9-SH {U.S. Fat. No. 4,424,219) (prepared by the reaction of maytansinoi with H2S or P2S5); (2) C-14-alkoxymethyl (demethoxy/CH2OR) (U.S. Pat. No. 4,33.1,598); (3) C-14-hydroxymethyl or acyloxymethyl (CH2OH or CH2OAc) (U.S. Pat. No. 4,450,254) (prepared from Nocardia); (4) C-15-hydroxy/acyioxy (U.S. Pat. No. 4,364,866) (prepared by the conversion of maytansinoi by Streptomyces); (5) C-15-.methoxy (U.S. Pat. Nos. 4,313,946 and 4,315,929) (isolated from Trewia nudiflora), (6) C-.1 8-N-demethyl (U.S. Pat Nos. 4,362,663 and 4,322,348) (prepared by the demettrylation of maytansinoi by Streptomyces); and (7) 4,5-deoxy (U.S. Pat. No 4,371,533) (prepared by the titanium trichloride/UAH reduction of maytansinoi). The cytotoxic conjugates may be prepared by in vitro methods. To link a cytotoxic agent, drug or prodrug Jo the antibody, commonly, a linking group is used. Suitable linking groups are known in the art and include disulfide groups, thioether groups, acid labile groups, photolabile groups, peptidase labile groups and esterase labile groups. For example, conjugates can be constructed using a disulfide exchange reaction or by forming a thioether bond between an antibody of interest and the drug or prodrug. The molecule conjugated to an antibody of interest can be a molecule with a pharmacologic activity, such as a drug, such as a small molecule or a biologic. Thus, die biologic can be a cytokine, for example. The molecule can be a prodrug, such as a drug ester. The molecule can be a radionuclide. As discussed above, the instant invention provides isolated nucleic acid sequences encoding an antibody or functional variant thereof as disclosed herein, vector constructs comprising a nucleotide sequence encoding the extended Type 1 giyeosphingolipid-binding polypeptides of the present invention, host cells comprising such a vector, and recombinant techniques for the production of the polypeptide thai binds extended Type I glycosphingoltpids. The vector normally contains components known in the art and generally include, but are not limited to. one or more of the following: a signal sequence, an origin of replication, a promoter, a poly A sequence, one or more marker or selection genes, sequences facilitating and/or enhancing translation, an enhancer element and so on. Thus, the expression vectors include a nucleotide sequence operably linked to such suitable transcriptional or translational regulatory nucleotide sequences such as those derived from mammalian, microbial, viral or insect genes. Examples of additional regulatory sequences include operators, mRNA ribosomal binding sites, and/or other appropriate sequences which control transcription and translation, such as initiation and termination thereof. Nucleotide sequences are "operably linked" when die regulatory sequence functionally relates to the nucleotide sequence for the appropriate polypeptide. Thus, a promoter nucleotide sequence is operably linked to, e.g., the antibody heavy chain sequence if the promoter nucleotide sequence controls the transcript! on of that nti c! eotide sequence. In addition, sequences encoding appropriate signal peptides that are not naturally associated with antibody heavy and/or light chain sequences can be incorporated into expression vectors. For example, a nucleotide sequence for a signal peptide (secretory leader) may be fused in-frame to the polypeptide sequence so thai the antibody is secreted to the periplasniic space or into the medium. A signal peptide that is functional in the intended host cells enhances extracellular secretion of the appropriate antibody or portion thereof. The signal peptide may be cleaved from the polypeptide on secretion of antibody from the cell. Examples of such secretory signals ate welt known and include, e.g., those described in U.S. Pat. Mos. 5,698,435; 5,698,417; and 6,204,021 The vector may be a plasmid, a singie-stranded or double-stranded viral vector, a singie-stranded or double-stranded RNA or DNA phage vector, a phagemid, a cosnud or any other carrier of a transgene of interest. Such vectors may be introduced into cells as polynucleotides by well known techniques for introducing DNA and RNA into cells. The vectors, in the case of phage and viral vectors also may be introduced into cells as packaged or encapsulated virus, or a vims-tike particle by well known techniques for infection and transduction- Viral vectors may be replication competent or replication defective. In the latter case. vim) propagation generally will occur only in complementing host cells and using plural vectors carrying the various virus components necessary to produce a particle. Cell-free translation systems may also be employed to produce the protein using RNAs derived from the present DNA constants of interest (see, e.g., WO 86/05807 and WO 89/01036; and U.S. Pat. No. 5,122;464). The antibodies of the present invention can be expressed from any suitable host cell. Examples of host cells useful in the instant invention include prokaryotic, yeast or eokaryotic cells and include but are not limited to microorganisms such as bacteria (e.g., B. coli, B. subtil is, Enterobacter, Erwinia. Klebsiella, Proteus, Salmonella, Serratia and Shigella, as well as Bacilli, Pseudomonas and Streptomyces) transformed with recombinant bacteriophage DNA, plasmid DNA or cosroid DNA expression vectors containing the antibody coding sequences of interest; yeast (e.g., Saccharomyces, Pichia, Actinomycetes, Kluyveromyces, Schizosaccharomyces, Candida, Trichoderma, Neurospora, and filamentous fungi, such as Neurospora, Penicillium, Tolypocladium and Aspergillus) transformed with recombinant yeast expression vectors containing antibody coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., Baculovirus) containing antibody coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus. CaMV; or tobacco mosaic virus. TMV) or transformed with recombinant plasmid expression vectors (e.g.. Ti plasmid) containing antibody coding sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293 or 3T3 cells) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; or the vaccinia virus 7.5K promoter). Expression vectors for use in prokaryolic host cells generally comprise one or more phenotypic selectable marker genes. A phenotypie selectable marker gene is, for example, a gene encoding a protein thai confers antibiotic resistance or that supplies an autotrophic requirement. Examples of useful expression vectors for prokaryotic host cells include those derived from commercially available plasmids, such as pKK223-3 (Pharmacia Fine Chemicals, Uppsala, Sweden), pGEMl (Promega Biotec, Madison, WI), pET (Novagen, Madison, Wl) and the pRSET (mvitrogert Carlsbad, CA) series of vectors (Sludier, i Mol Biol 219:37 (1991); and Schoepfer, Gene 124:83 (1993)}. Promoter sequences commonly used for recombinant prokaryotic host cell expression vectors include T7 (Rosenberg et al.. Gene 56:125 (1987)), p-lactamase (penicillinase), lactose promoter (Oumg et al.s Nature 275:615 (1978); and Goeddel et al, Nature 281:544 (1979)), tryptophan (trp) promoter system (Goeddel et al., NucI Acids Res 8:4057 (1980)), and tac promoter (Sambrook et al., Molecular CLoning, A Laboratory Manual, 2nd ed.. Cold Spring Harbor Laboratory (1990)). Yeast vectors will often contain an origin of replication sequence, such as, from a 2ft yeast plasmid, an autonomously replicating sequence (ARS), a promoter region, sequences for poiyadenylation. sequences for transcription termination, and a selectable marker gene. Suitable promoter sequences for yeast vectors include, among others, promoters for metallorlvlonem, 3-phosphogtycerate .kinase (Hitzeman etal., .1 Biol Chem 255:2073 (1.980)) or other glycolytic enzymes (Holland et al„ Biochem 17:4900 (1978)) such as enolase, glycerakU4rydes-3-phosphate dehydrogenase, bexokinase. pyruvate decarboxylase, phosphofruclokmase, glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triosephosphate isomerase, phosphoglucosc isomerase and glucok.imise, Other suitable vectors and promoters for use in yeast expression are further described in Fleer et al„ Gene 107:285 (1991). Other suitable promoters and vectors for yeast and yeast transformation protocols are well known in die art. Yeast transformation protocols are well known. One such protocol is described by llinnen et a.L Proe Natl Acad Sci 75:1929 (1978), which selects for Trp; tmnsibmuyms in a selective medium. Any eukaryotic cell culture is workable, whether from vertebrate or invertebrate culture. Examples include plant and insect cells (Luckow et a!., Bio/Technoiogy 6;47 (1988); Miller et al., Genetic Engineering, Setlow et at, eds., vol. 8, pp. 277-9, Plenum Publishing (1986); and Maeda et al. Nature 315:592 (1985)). For example, Baculovirus systems may be used for production of heterologous proteins. In an insect system, Autographs caliJbmica nuclear poiyhedrosis virus (AcNPV) may be used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. The antibody coding sequence may be cloned under control of an AcNPV promoter (far exampie, the polyhedrin promoter). Other hosts that have been identified include Aedes, Drosophila roelanogasier and Bombyx mori. A variety of viral strains for transfection are publicly available, e.g., the L-l variant of AcNPV and the 8m-5 strain of Bombyx mori NPV. Moreover, plant cell cultures of cotton, corn, potato, soybean, petunia, tomato, algae, duckweed and tobacco can also be utilized as hosts, as known in the art. Vertebrate cells, and propagation of vertebrate cells, in culture (tissue culture) can be a routine procedure, although fastidious celt lines do exist which require, for example, a specialized medium with unique factors, feeder cells and so on, see Tissue Culture, Kruse et al, eds., Academic Press (1973). Examples of useful mammal host, cell lines are monkey kidney; human embryonic kidney; baby hamster kidney; Chinese hamster ovary (CHO, llrlauh et al., Proc Natl Acad Sci USA 77:4216 (1980)); mouse Sertoli; human cervical carcinoma (for example, HeLa), canine kidaey; human lung; human liver; mouse mammary tumor; and NSO cells. Host ceils are transformed with vectors for antibody production and cultured in conventional nutrient medium containing growth factors, vitamins, minerals and so on, as well as inducers appropriate for the cells and vectors used. Commonly used promoter sequences and enhancer sequences are derived, for example, from polyoma virus. Adenovirus 2. Simian virus 40 (SV40) and human cytomegalovirus (CMV). DNA sequences derived from the SV40 viral genome may 58 2 5 FEB 2011, be used to provide other genetic elements for expression of a structural gene sequence in a mammalian host cell, e.g., SV40 origin, early and late promoter, enhancer, splice and polyadenylation sites. Viral early and late promoters are particularly useful because both are easily obtained from a viral genome as a fragment which may also contain a viral origin of replication. Exemplary expression vectors for use in mammalian host cells are commercially available. Commercially available medium such as Ham's HO, Minimal Essential Medium (MEM), RPMI-1640 and Dnlbecco's Modified Eagle's Medium (DMEM) are suitable for cuituring host cells,in addition, any of the media described in Ham et a!., Vleih Enzymol 58:44 (1979) and Barnes et ai., Anal Biochem 102:255 (1980), and in U.S. Fat. Nos. 4,767,704; 4,657,866; 4,560,655; 5,122,46.9; 5,712,163; or 6,048,728 may be used as a culture medium for the host ceils. Any of those media may be supplemented as necessary with hormones and/or other growth factors (such as insulin, transferrin or epidermal growth factor), salts (such as chlorides, such as sodium, calcium or magnesium chloride; and phosphates), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics, trace elements (which may be defined as inorganic compounds usually present at final concentrations in the imcromolar range) and glucose or an equivalent energy source. Any other necessary supplements may be included at appropriate concentrations, as a design choice. The culture conditions, such as temperature, pH and the like, are as known in the art appropriate for the cell and to enable the desired expression of the transgene. The polynucleotides of interest may be obtained, and the nucleotide sequence of the polynucleotides determined, by any method known in the art. For example, if the nucleotide sequence of the antibody is known, a polynucleotide encoding the antibody may be assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier et ai.. Bio/Techniques 17:242 (1994)) and then amplifying the Jigated oligonucleotides, for example, by PCR. Alternatively, a polynucleotide encoding an antibody may be generated from nucleic acid of a cell expressing same. If a clone containing a nucleic acid encoding a particular antibody is not available, bat the sequence of the antibody molecule is known, a nucleic acid encoding the immunoglobulin may be obtained from a suitable source, such as a library, which may be one specific for antibody-producing cells, such as hybridoma cells selected to express an antibody of the invention. Suitable primers can be configured for PCR amplification. Amplified nucleic acids generated by PCR may then be cloned into replicable cloning vectors using any method known in the art. Once tiie nucleotide sequence and corresponding amino acid sequence of the antibody are determined, the nucleotide sequence of the antibody may be manipulated to obtain the equivalents of interest described herein using methods known in the art for manipulating nucleotide sequences, e.g., recombinant DNA techniques, site directed mutagenesis. PCR etc. (see, for example, Sambrook.et a!., Molecular Cloning, A Laboratory Manual, 2nd ed.. Cold Spring Harbor Laboratory (1.990); and Ausubel et al., eds.. Current Protocols in Molecular Biology, John Wiley & Sons (1998)) to generate antibodies having a different amino acid sequence, for example, to create amino acid substitutions, deletions and/or insertions. The amino acid sequence of the heavy and/or light chain variable domain may be inspected to identify the sequences of the CDR's by well known methods, e.g., by comparison to known amino acid sequences of other heavy and light chain variable regions to determine the regions of sequence hyper variability. Using routine recombinant DNA techniques, one or more of the CDR's may be inserted within framework regions, e.g., into human framework regions to humanize a non-human antibody, as described supra. The polynucleotide of interest generated by the combination of the framework regions and one or more CDR's, encodes a molecule that specifically binds extended Type 1 glycosphtngolipid, or at least the carbohydrate epitopes and structure recognized thereby. For example, such methods may be used to make amino acid substitutions or deletions of one or more cysteine residues participating in an intrachain disulfide bond to generate antibody molecules lacking one or more intrachain disulfide bonds. The antibodies or antibody fragments of the invention can be used to detect extended Type i glycosphingolipid, and hence cells expressing extended Type I glycosphingolipid, in a biological sample in vitro or in vivo. In one embodiment, the anti-extended Type I glycosphmgolipid antibody of the invention is used to determine presence of and die level of extended Type 1 glycosphingolipid in a tissue or in ceils derived from the tissue. The levels of extended Type I glycosphingolipid in the tissue or biopsy can be determined, for example, in an immunoassay with the antibodies or antibody fragments of the invention. The tissue or biopsy thereof can be frozen or fixed. The same or other methods can be used to determine oilier properties of extended Type 3 glycosphingolipid, such as the level diereof, cellular localization and so on. The above-described method can be used, for example, to diagnose a cancer in a subject known to have or suspected to have a cancer, wherein the level of extended1 Type 1 grycospftrngoKpfcf measitred in said patient is compared withr at of a normal reference subject or standard. The instant invention further provides for monoclonal antibodies, humanized antibodies and epHope-bhiding fragments thereof that are further labeled for use in research or diagnostic applications. In some embodiments, the label is a radiolabel, a fluorophoie. a chromophore, an imaging agent or a metal ion, for example, A method for diagnosis is also provided in which said labeled antibodies or epitope-binding fragments thereof are administered to a subject suspected of having a cancer, arthritis, autoimmune diseases or other diseases related to, caused by or associated with extended Type t glycosphingolipid expression and/or function. and the distribution of the label within the body of the subject is measured or monitored. The antibody and fragments thereof of the instant invention may be used as affinity purification agents, hi that process, the antibodies are immobilized on a solid phase, such as a dextran or agarose, resin or filter paper, using methods known in the art. The immobilized antibody is contacted with a sample containing For diagnostic applications, the antibody of interest typically will be labeled with a detectable moiety or marker. Numerous labels are available which can be generally grouped into the following categories: (a) radioisotopes, such as 36S, 14C, 125l ;,3H and ' lI (the antibody can be labeled with the radioisotope using a technique described in, for example, Current Protocols in Immunology, vol. 12, Coligen et aL ed, Wiley-lnterscience, New York (1991), and radioactivity can be chelates (europium chelates), fluorescein and derivatives thereof, rhodamine and derivatives thereof, dansyl, lissamine, phyeoerythrin and Texas Red, the fluorescent labels can be conjugated to the antibody using a technique disclosed in Current. Protocols in Immunology, supra, for example, where fluorescence can be quantified using a fluorimeter; and (c) various enzyme substrate labels are available (U.S. Pat. No. 4,275,149 provides a review), the enzyme generally catalyzes a chemical alteration of a chromogenic substrate which can be measured using various techniques, for example, the enzyme may catalyze a Color change in a substrate, which can be measured spectrophotoinetrically, or the enzyme may alter the fluorescence or ehemiluminescenee of the substrate. Techniques for quantifying a change in fluorescence are known, for example, using a humnometer, or the label donates energy to a fluorescent acceptor. Examples of enzymatic labels include luciferases (e.g., firefly luciferase and bacteria! luciferase; U.S. Pat. No. 4/737,456), luctferin, 2,3-dihydrophthalazinediones, malate dehydrogenase, urease, peroxidase, such as horseradish peroxidase (HRPO), alkaline phosphatase, p"-galactosidase, glucoarnylase, lysozyme. saccharide oxidases (e.g., glucose oxidase, galactose oxidase and g!ucose-6-phosphate dehydrogenase), heterocyclic oxidases (such as uricase and xanthine oxidase), lactoperoxidase, inicroperoxidase and the like. Techniques for conjugating enzymes to antibodies are described in O'Sullivan et al„ Meth Enz, ed. Langone & Van Vtinakis, Academic Press, New York, 73 (1981). When such labels are used, suitable substrates are available, such as: (i) for horseradish peroxidase with hydrogen peroxidase as a substrate, wherein the hydrogen peroxidase oxidizes a dye precursor (e.g., onhophenylene diamine (OPD) or 3,.V,5.,5'-ietrarriethyl benzidine hydrochloride (TMB)); (ii) for alkaline phosphatase (AP) with p-nitrophenyt phosphate as the chromogemc substrate; and (iii) (βJ-D-galactosidase (β-D-Gal) with a chromogenic substrate (e.g., p-nitrophenyl-β-D-galactosidase) or a fluorogenic substrate such as, 4-methy 1 umbel li fery 1-p1- D-ga iactosi dase. Other enzyme-substrate combinations are available to those skilled in the art For a generai review, see U.S. Pat. N'os. 4,27SJ49 md 4,318,980. Sometimes, the label is indirectly conjugated with the antibody. For example, the antibody can be conjugated with biotin and any of the reporters mentioned above can be conjugated with avidin, or vice versa. Biotin binds selectively to avidin and thus, the label can be conjugated with the antibody in that indirect manner. Various avidins are known in the art. Alternatively, to achieve indirect conjugation of the label, the antibody can be conjugated with a small hapten (e.g., digoxin) and one of the different, types of labels or reporters mentioned above is conjugated with an anti-digoxin antibody. Thus, indirect conjugation of the label widi the antibody or mutein can be achieved using a second antibody. In another embodiment of the invention, the antibody need not be labeled, and the presence thereof can be detected using a labeled antibody which binds to the antibody, another form of a second antibody. The antibodies of the present invention may be employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipifation assays. Zola, Monoclonal Antibodies: A Manual of Techniques (CRC Press. Inc. 1987). Competitive binding assays rely on the ability of a labeled standard to compete with the test sample for binding with a limited amount of antibody. The amount of antigen in the test sample is inversely proportional to the amount of standard that becomes bound to the antibodies. To facilitate determining the amount of standard that becomes bound, the antibodies generally are insolubilized before or after the competition. As a result, the standard and test sample that are bound to the antibodies may conveniently be separated from the standard and test sample which remain unbound-Sandwich assays involve the use of two antibodies, each capable of binding to a different immunogenic portion, determinant or epitope, of the target to be detected, in a sandwich assay, the test sample to be analyzed is bound by a first antibody which is immobilized directly or indirectly on a solid support, and thereafter a second antibody directly or indirectly labeled binds to the bound test sample, thus forming an insoluble three-part complex, see e.g., U.S. Pat. No. 4,376,110. The second antibody may itself be labeled with a detectable moiety (direct sandwich assays.) or may be measured using an anii-inummoglobuKn antibody or other suitable member of the binding pair (antibody/antigen, receptor/ligand, enzyme/substrate, for example) that is labeled with a delectable moiety (indirect sandwich assay). For example, one type of sandwich assay is an EL1SA assay, in which case the detectable moiety is an enzyme. For immunohistochemistry, the cell or tissue sample may be fresh or frozen or may be embedded in paraffin and fixed with a preservative such as formalin, for example, The antibodies may also be used for in vivo diagnostic assays. Generally, the antibody or variant thereof is labeled with a radionucleotide (such as 111 10. 99Tc, 14,C,131, 3H- 32P or 35S) so that the sites expressing extended Type 1 glycosphinsolipid can be localized using, for example, inimimoscintigraphy and a gamma camera. The instant invention also includes kits, e.g. comprising an antibody, fragment thereof, homolog, derivative thereof and so on. such as a labeled or cytotoxic conjugate, and instructions for the use of the antibody, conjugate for killing or labeling particular cell types and so on. The instructions may include directions for using the antibody, conjugate and so on in vitro, in vivo or ex vivo. The antibody can be in liquid form or as a solid, generally lyophitized. The kit can contain suitable other reagents, such as a buffer, a reconstituting solution and other necessary ingredients for the intended use. A packaged combination of reagents in predetermined amounts with instructions for use thereof such as, for a therapeutic use for performing a diagnostic assay is contemplated. Where the antibody is labeled, such as with an enzyme, the kit can include substrates and cefaclors required by die enzyme (e.g., a substrate precursor which provides the detectable chromophore or fluorophore). In addition, other additives may be included such as stabilizers, buffers (e.g., a block buffer or lysis buffer) and the like. The relative amounts of the various reagents may be varied to provide for concentrates of a solution of a reagent, whkb.pvovid.es user flexibility, economy of space, economy of reagents and so on. The reagents may be provided as dry powders, usually iyophilized, including excipients, which on dissolution provide a reagent solution having the appropriate concentration. The antibodies of the present invention may be used to treat a mammal. In one embodiment, the antibody or equivalent of interest is administered to a nonhuroan mammal for the purposes of obtaining preclinical data, for example. Exemplary nonhuman mammals to be treated include nonhuman primates, dogs. cats, rodents and other mammals in which preclinical studies are performed. Such mammals may be established animal models for a disease to be treated with the antibody, or may be used to study toxicity of the antibody of inter est. .in each of those embodiments, dose escalation studies may be performed in the mammal. The product of interest may have therapeutic use in those animals as well An antibody, with or without a second component, such as a therapeutic moiety conjugated to same, administered alone or in combination with a cytotoxic factor(s) can be used as a therapeutic. The present invention is directed to antibody-based therapies which involve administering antibodies of the invention to an animal, a mammal or a human, for treating an extended Type 1 glycosphingohpid-mediated or associated disease, disorder or condition. The animal or subject may be a mammal in need of a particular treatment, such as a mammal having been diagnosed with a particular disorder, e.g., one relating to extended Type I giycosphingolipid, or associated with abnormal extended Type I chain structure expression and function . Antibodies directed against extended Type I gtycosphingolipid are useful, for example, for prophylaxis or treatment of cancer and autoimmune disorders, for example. For example, by administering a therapeutically acceptable dose of an ami-extended Type I glycosphingolipid antibody of the instant invention, or a cocktail of a p1oraliry of the instant antibodies or equivalents thereof, or in combination with other antibodies of varying sources, or in combination with a non-antibody drug, such as, an anfi-in.fiammatory drug, a cytotoxic agent, an antibiotic and so on, such as, a platinum drug, methotrexate and so on, tosease symptoms maybe ameliorated or prevent in ifofcireateA mtflnrntft, particularly humans. Therapeutic compounds of the invention include, but are not limited to, antibodies of the invention (including fragments, analogs, equivalents and derivatives thereof as described herein) and nucleic acids encoding antibodies of the invention as described herein (including fragments, analogs and derivatives thereof) and anti-idiotypic antibodies as described herein, the antibodies of the invention can be used to treat, inhibit or prevent diseases, disorders or conditions associated with aberrant expression and/or activity of extended Type I glycosphingolipid, including, but not limited to, any one or more of the diseases, disorders, or conditions described herein. The treatment and/or prevention of diseases, disorders or conditions associated with aberrant expression and'or activity of extended Type I glycosphingolipid includes, but is not limited to, alleviating at least one symptom associated with those diseases, disorders, or conditions. Antibodies of the invention may be provided in pharmaceutical I y acceptable compositions as known in the art. or as described herein. The term "physiologically acceptable," "pharmacologically acceptable," "phanrjaceutically acceptable." and so on means approved by a regulatory agency of the Federal or a stale government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals and more particularly in humans. The anti-extended Type 1 glycosphingofipid antibody can be administered to a mammal in any acceptable manner. Methods of introduction include, but are not limited to, parenteral, subcutaneous, intraperitoneal, intrapulmonary, intranasal epidural, inhalation and oral routes, and if desired for immunosuppressive treatment, imralesional administration. Parenteral infusions include intramuscular, intradermal, intravenous, intraarterial or intraperitoneal administration. The antibodies or compositions may be administered by any convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa etc.) and may be administered together with other biologically active agents. Administration can be systemic or local. la addition, it may be desirable to introduce the therapeutic antibodies or compositions of the invention into the central nervous system by any suitable route, including intraventricular and intrathecal injection; intraventricular injection may be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Oinmaya reservoir. In addition, the antibody can be suitably administered by pulse infusion, particularly with declining doses of the antibody. Preferably the dosing is given by injection, preferably intravenous or subcutaneous injections, depending, in part, on whether the administration is brief or chronic. Various other delivery systems are known and can be used to administer an antibody of ihe present invention, including, e.g., encapsulation in liposomes, microparticles, microcapsules and so on (see Langer, Science 249:1527 (1990)); expression of an antibody, mutein thereof or antigen-binding portion thereof, of interest on a liposome, particle, capsule and so on to yield a targeting vehicle, Treat et al, in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein et al.. eds., p. 353-365 (1989); and Lopez-Berestein, ibid., p. 317-327; recombinant, cells capable of expressing tire compound, see, e.g., Wu et al, J Bio Cliem 262:4429 (1987); construction of a nucleic acid as part of a retroviral or other vector; and so on. The active ingredients may also be entrapped in a microcapsule prepared, for example, by coascervation techniques or by interfactal pot.ynierizat.ion, for example, hydroxymethylcellulose or gelatin-microcapsule and poly-(memylmetb.acylate) microcapsule, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nanopariicles and nanocapsutes) or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences, 16th edition, A. Osat Ed, {1980). When the liposome or particle expresses an antibody of interest, any of a variety of compounds can be carried in the liposome, such as, a non-antibody drug, small molecule drug and so on. The instant antibody can thus serve a targeting function. Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent. The antibody may also be administered into the lungs of a patient in the form of a dry powder composition, see e.g.= U.S. Pat. No. 6,514,496. In a specific embodiment, it may be desirable to administer the therapeutic antibodies or compositions of the invention locally to the area in need of treatment; that may be achieved by. for example, and not by way of limitation, local infusion, topical application, by injection, by means of a catheter, by means of a suppository or by means of an implant; said implant being of a porous, non-porous or gelatinous material, including membranes, such as sialastic mc-nibranus or fibers. Preferably, when administering an antibody of the invention, care is taken to use materials to which the protein does not absorb or adsorb. In yet another embodiment, the antibody can be delivered in a controlled release system. In one embodiment, a pump may be used (see Langer, Science 249:1527 (.1990), Sefton, CRC Crit Ref Biotned E«g 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); and Saudek et al., N Engl J Med 321:574 (1989)). In another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release, linger et al., eds., CRC Press (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smofen et at., eds.> Wiley (1984); Ranger et a]., J Macromol Sci Rev Macromol Chem 23:61 (1983); see also Levy etal., Science228:190 (1985); Duringetal., Ann Neurol25:351 (1989); and Howard et al, J Meurosurg 71:105 (1989)). In yet another embodiment, a controlled release system can be placed in proximity of the therapeutic target. Sustained-release preparations maybe prepared. Suitable examples of sustained-release preparations include semi-permeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g.. films or matrices. Examples of sustained-release matrices include polyesters, bydrogels (tor example, poly(2-hydroxyethylmethaciylate), poly(vmylalcohol)), polylactvdes (U.S. Pat. No. 3,773,919), copolymers of L-glutarmc acid and ethyt-L-glutamate, non-degradable etlrylene-vinyl acetate. degradable lactic acid-glycolic acid copolymers (such as, injectable microspheres composed of lactic acid-glycolic acid copolymer) and po!y-D-(->3-hydroxybutyiic acid. While polymers such as ethyleue-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. Rational strategies can be devised for stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S-S bond formation through thio-disulfide interchange, stabilization maybe achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, amino acid substitution and developing specific polymer matrix compositions. Therapeutic formulations of the polypeptide or antibody may be prepared for storage as lyophilized formulations or aqueous solutions by mixing die polypeptide having the desired degree of purity with optional "pharmaceuticalVy acceptable" carriers, diluents, excipients or stabilizers typically employed in the art, i.e., buffering agents, stabilizing agents, preservatives, isotonifiers, non-ionic detergents, antioxidants and other miscellaneous additives, see Remington's Pharmaceutical Sciences, 16th ed, OsoL ed. (1980). Such additives are generally nontoxic to the recipients at the dosages and concentrations employed, hence, the cxcipiems, diluents, carriers and so on are pharmaceutically acceptable. An "isolated" or "pug proteins from the cell or tissue source or medium from which the protein is derived, or substantirified" antibody is substantially free of cellular material or other contaminatinally free of chemical precursors or other chemicals when chemically synthesized. lire language "substantially free of cellular material" includes preparations of an antibody in which the polypeptide/protein is separated from cellular components of the cells from which same is isolated or recombinantly produced. Thus, an antibody that is substantially free of cellular material includes preparations of die antibody having less than about 30%, 20%, 10%, 5%, 2.5% or i%, (by dry weight) of contaminating protein or cellular or subcellular material. When the antibody is recombinantly produced, it is also preferably substantially free of cxriture medium, i.e medimn represents less than about 20%, 10%, 5%, 2.5% or 1 % of the volume of the protein preparation. When antibody is produced by chemical synthesis, it is preferably substantially free of chemical precursors or other chemicals and reagents, i.e., the antibody of interest is separated from chemical precursors or other chemicals which are involved in the synthesis of the protein. Accordingly, such preparations of the antibody have less than about 30%, 20%, 10%, 5% or 3% (by dry weight) of chemical precursors or compounds other than antibody of interest. In a preferred embodiment of the present invention, antibodies are isolated or purified. As used herein, the phrase "low to undetectable levels of aggregation" refers lo samples containing no more than 5%, no more than 4%, no more than 3%, no more than 2%, no more than 1% and often no more than 0.5% aggregation of antibody or variant thereof, that is, two or more antibody molecules or variants thereof joined or coalesced together, by weight protein, as measured by, for example, high performance size exclusion chromatography (HPSBC). As used herein, the term "low to undetectable level, 90%,s of fragmentation" refers to samples containing equal to or more than 80%, S5% 95%, 98% or 99% of intact antibody molecule or variant thereof, of the total protein, for example. in a single peak, as determined by HPSEC, or in two (2) peaks (heavy chain and light chain) by, for example, reduced capillary gel electrophoresis (rCGE) and containing no other single peaks having more than 5%, more than 4%, more than 3%, more than 2%, more than 1% or more than 0.5% of the total protein, each. The rCGE as used herein refers to capillary gel electrophoresis under reducing conditions sufficient to reduce disulfide bonds in an antibody or antibody-type or derived molecule. The instant invention provides methods for preparing liquid formulations of the antibody or extended Type 1 gtycosphingolipid-binding fragment thereof, said methods comprising concentrating a fraction of purified antibody to a final concentration of about 15 mg/ml, about 20 mg/ml, about 30 mg/ml, about 40 mg/ml, about 50 mg/ml, about 60 mg/ml, about 70 mg/ml, about 80 mg/ml about 90 mg/ml, about 100 mg/ml, about 200 mg/ml, about 250 mg/ml, about 300 mg/ml or more using, for example, a semi-permeable membrane with an appropriate molecular weight (raw) cutoff (e.g., 30 kD cutoff for F(ab)2 fragments thereof: and 10 kD cutoff for Fjh fragments) and, optionally, diafiltering the concentrated antibody traction into the formulation buffer using the same membrane. In addition, the present invention also encompasses stable liquid formulations of the products of interest that can have improved half-life in vivo. Thus, the antibody of interest has a half-life in a subject, preferably a human, of greater than 3 days, greater than 7 days, greater than 10 days, greater than 15 days, greater than 25 days, greater than 30 days, greater than '3eater than 3 months, greater than A months, greater than 5 months or m5 days, greater than 40 days, greater than 45 days, greater than 2 months, grore. As used herein, the terms "stability" and "stable" in the context of a liquid formulation comprising an extended Type 1 glycosphtngolipid antibody or binding fragment thereof refer to the resistance of the antibody or antigen-binding fragment thereof in the formulation to thermal and chemical unfolding, aggregation, degradation or fragmentation under given manufacture, preparation, transportation and storage conditions. The "stable" formulations of the invention retain biological activity equal to or more than 80%, 85%, 90%, 95%, 98%, 99% or 99.5% under given manufacture, preparation, transportation and storage conditions. The stability of said antibody preparation can be assessed by degrees of aggregation, degradation or fragmentation by methods known to those skilled in the art, including, but not limited to, rCGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and HPSEC. compared to a reference, for a predetermined period of time under selected storage conditions as a design choice. The instant invention encompasses liquid formulations having stability at temperatures found in a commercial refrigerator or freezer found in the office of a physician or laboratory, such as from about -20° C to about 5° C, said stability assessed, for example, by high performance size exclusion chromatography (HPSEC), for storage purposes, such as, for about 60 days, for about 120 days, for ' about 180 days, for about a year, for about 2 years or more. The liquid formulations of the present invention also exhibit stability, as assessed, for example, by H'SPEC, at room temperatures, for at least a few hours, such as about one hour, about two hours or about three hours prior to use. The term, "carrier," refers to a diluent, adjuvant, excipient or vehicle with which the therapeutic is administered. Such physiological carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil. mineral oil, sesame oil and the like. Water is a suitable carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions also can be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethano! and the like, The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The compositions can take the form of solutions, suspensions, emulsions, tablets, pills, capsules, powders, sustained-release formulations, depots and the like. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral fortmilations can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate etc., flavorants, colorants, odorants and so on. Examples of suitable carriers are described in "'Remington's Pharmaceutical Sciences," Martin. Such compositions will contain an effective amount of the antibody, preferably in purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the patient. As known in the art, the formulation will be constructed to suit tlie mode of administration. Buffering agents help to maintain the pH in a range which approximates physiological conditions or conditions conducive to antibody stability. Buffers are preferably present at a concentration ranging from about 2 mM to about 50 mM. Suitable buffering agents for use with the instant invention include both organic and inorganic acids, and salts thereof, such as, for example, citrate buffers (e.g., monosodium citrate-disodium citrate mixture, citric acid-trisodium citrate mixture, citric add-monosodium citrate mixture etc.), succinate buffers (e.g., succinic acid-roonosodiuni succinate mixture, succinic acid-sodmm hydroxide mixture, succinic acid-disodium succinate mixture etc.). tartrate buffers (e.g., tartaric acid-sodium tartrate mixture, tartaric acid-potassium tartrate mixture, tartaric acid-sodium hydroxide mixture etc.). fumarate buffers (e.g.. fumaric acid-monosodium fumarate mixture, fumaric acid-disodium fumarate mixture, monosodium fiunarate-disodium fumarate mixture etc.), gluconate buffers (e.g., gluconic acid-sodium glyconate mixture, gluconic acid-sodium hydroxide mixture, gluconic acid-potassium gluconate mixture etc.), oxalate buffers (e.g., oxalic acid-sodium oxalate mixture, oxalic acid-sodium hydroxide mixture, oxalic acid-potassium oxalate mixture etc.), lactate buffers (e.g., lactic acid-sodium lactate mixture, lactic acid-sodium hydroxide mixture, lactic acid-potassium lactate mixture etc.) and acetate buffers (e.g., acetic acid-sodium acetate mixture, acetic acid-sodium hydroxide mixture etc.). Phosphate buffers, carbonate buffers, histidine buffers, trimethylamine salts such as Tris, HEPES and other such known buffers can be used. Preservatives may be added to retard microbial growth, and may be added in amounts ranging from about 0.2% to about. 1 % (w/v). Suitable preservatives for use with the present invention include phenol, benzyl alcohol, m-cresol, methyl paraben, propyl paraben, octadecyldimethyl benzyl ammonium chloride, benzylconium halides (e.g., chloride, bromide and iodide), hexamethonium chloride, alky! parabens, such as, methyl or propyl paraben, catechol, resorcinoi, cyclohexanol and 3-pentanol. Isotonicifiers are present to ensure physiological isotonicity ofliquid compositions of the instant invention and include poihydric sugar alcohols, such as, trihydric or higher sugar alcohols, such as glycerin, erythrirol, arabitol, xylitol, sorbitol and irtannitol. Poiyhydric alcohols can be present in an amount of between about 0.1% to about 25%, by weight, preferably about 1 % to about 5% taking into account the relative amounts of the other ingredients. Stabilizers refer to a broad category of excipients which can range in function from a bulking agent to an additive which solubitizes the therapeutic agent or helps to prevent denaturation or adherence to the container wall. Typical stabilizers can be poiyhydric sugar alcohols; amino acids, such as arginine, lysine. glycine, glutamhie, asparagine, histidine, alanine, ornithine, L leucine, 2-phenylaianine, glutamic acid, threonine etc.; organic sugars or sugar alcohols, such as lactose, trehalose, stachyose, arabitol erytb.rUol, manrritol sorbitol, xylitol, libitol, royoinisitot, galactkot, glycerol and the like, including cyditols such as inositol; polyethylene glycol; amino acid polymers; sulfur containing reducing agents, such as urea, glutathione, thiocric acid, sodium thioglycolate, thioglycerol, a-inonodvioglycerol and sodium thiosulfate; Sow molecular weight polypeptides (i.e., •'10 residues); proteins, such as human serum albumin, bovine serum albumin, gelatin or immunoglobulins; hydrophilic polymers, such as polyvinylpyrrolidone, saccharides, monosaccharides, such as xylose, mannose, fructose, glucose; disaccharides, such as lactose, maltose and sucrose: trisaccharides such as rafftnose; polysaccharides such as dextran and so on. Stabilizers can be present in the range from about 0.1 to about 10,000 w/w per part of active protein. Additional miscellaneous excipients can include bulking agents, (e.g., agar, gelatin, starch and so on), chelating agents {e.g., EDTA), antioxidants (e.g., ascorbic acid, methionine or vitamin E) and cosolvents. As used herein, the term "surfactant" refers to organic substances having amphipathic structures, namely, are composed of groups of opposing solubility tendencies, typically an oil soluble hydrocarbon chain and a water soluble ionic-group. Surfactants can be classified, depending on the charge of the surface active moiety, into anionic, cationic and nonionic surfactants. Surfactants often are used as wetting, emulsifying, solubilizing and dispersing agents for various pharmaceutical compositions and preparations of biological materials as those discussed herein. Non-ionic surfactants or detergents (also brown as "wetting agents") may be added to help solubilize the therapeutic agent, as well as to protect the therapeutic protein against agitation-induced aggregation, which also permits the formulation to be exposed to shear surface stresses without causing denaturation of the protein. Suitable non-ionic surfactants include polysorbates (20. SO etc.), polyoxamets (1S4, 188 etc.), Plutonic polyols and potyoxy ethylene sorbitan monoeihers (TWEEN-20 , TWEEN-80 etc.). Non-ionic surfactants may be present in a range of about 0.05 rag/ml to about 1.0 mg/ml, preferably about 0.07 mg/ml to about 0.2 mg/ml. As used herein, the term, "inorganic salt," refers to any compound, containing no carbon, that results from replacement of part or all of the acid hydrogen or an acid by a metal or a group acting like a metal, and often are used as a tonicity adjusting compound in pharmaceutical compositions and preparations of biological materials. The most common inorganic salts are NaCl, KCL NaHjPQ* etc. The present invention provides liquid formulations of an anti-extended Type 1 glycosplungoiipid-biudmg compound or fragment thereof, having a pH ranging from about 5.0 to about 7.0, or about 5.5 to 6.5, or about 5.8 to about 6.2, or about 6.0. The formulation herein also may contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely impact each other. For example, it may be desirable to further provide an immunosuppressive agent. Such molecules suitably are present in combination in amounts that are effective for the purpose intended. The formulation also can contain another drug, or a small molecule, a pharmacologic agent such as an anti-neoplastic drug, such as, cisplatin. The term "small molecule" and analogous terms include, but are not limited to, peptides, peptidomimetics, amino acids, amino acid analogues, organic compounds, pharmacologically active agents, such as drugs, polynucleotides. polynucleotide analogues, nucleotides, nucleotide analogues, organic or inorganic compounds (i.e., including heierorganic and/organometallic compounds) having a molecular weight less than about 10,000 grams per rnoie, organic or inorganic compounds having a moleculer weight less then about 5,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 1,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 500 grams per mole, and sahs, esters, and other pharmaeeutically acceptable forms of such compounds. Thus, in the case of cancer, the antibodies of the invention may be administered alone or in combination with other types of cancer treatments, including conventional chemotherapeuiic agents (paclitaxel, carboplatin, cisplatin and doxorubicin), anti-EGFR agents (gefiUmb, erlotinib and cet.uxi.mab), anfi-angigouesis agents (be-vacizumab and sunitinib), as well as immunoniodulating agents, such as interfeion-α and thalidomide. As used herein, the terms "therapeutic agent" and "therapeutic agents" refer to any agent(s) which can be used in the treatment, management or amelioration of a disease, disorder, malady and the like associated with aberrant extended Type 1 glycosphingoltpid expression, and metabolism in general, and activity. Also included are known compounds with a pharmacologic effect in treating a disorder and so on that is associated with aberrant extended Type I gtycosphingolipid expression, metabolism and activity- The antibody or variant, optionally, is fomulilated with one or more agents currently used to prevent or treat the disorder in question. The effective amount of such other agents depends on the amount of antibody present in the formulation, the type of disorder or treatment and other factors discussed above. These are generally used in the same dosages and with administration routes as used hereinbefore or about from t to 99% of the heretoforee employed dosages. The formulations to be used for in vivo administration must be sterile. That can be accomplished, for example, by filtration through sterile filtration membranes. For example, the liquid formulations of the present invention may he sterilized by filtration using a 0.2 urn or a 0.22 urn filter-In addition, the antibodies of the instant invention may be conjugated to various effector molecules such as heterologous polypeptides, drugs, radiomicleotides or toxins, see, e.g., WO 92/08495; \VO 93/14438; WO 89/L 2624; U.S. Pat. No. 5.314,995; and EPO 396,387. An antibody or fragment thereof maybe conjugated to a therapeutic moiety such as a cytoto (e-g. a cytostatic or cytoeidal agent), a therapeutic agent ox a radioactive metat ion (e.g., a emitters, such as, for example, 213Bi). A cytotoxin or cytotoxic ageftt includes any agent that is detrimental to cells. Examples include paclitaxol, cytochalasin B5 gramicidin D, ethidiiun bromide, emetine, mitomycin,, etoposide, t.enoPos' daunorubicin, daunomycin and doxorubicin), antibiotics (e.g., dactinomycin, actinomycin, bleomycin, mithramycin and anthramycin(AMC)), and anti-mitotic agents (e.g., vincristine and vinblastine). To prolong the serum circulation of an antibody in vivo, various techniques can be used. For example, inert polymer molecules, such as high molecular weight polyethylene glycol (PEG), can be attached to an antibody with or without a multifunctional tinker either through site-specific conjugation of the PEG to the N-terminus or to the C-terminus of the antibody or via Eamino groups present on lysine residues. Linear or branched polymer derealization that results in minimal loss of biologicalactivity can be used. The degree of conjugation can be closely monitored by SDS-PAGE and mass spectrometry to ensure proper conjugation of PEG molecules to the antibodies. Unreacted PEG can be separated from antibody-PEG conjugates by size-exclusion or by ion exchange chromatography. PEG-derivatized antibodies can be tested for binding activity as well as for in vivo efficacy using methods known to those of skilled in the art, for example, by immunoassays described herein. An antibody having an increased halt-life in vivo can also be generated by introducing one or more amino acid modifications (i.e., substitutions, insertions or deletions) into an igG constant domain, or FCR binding fragment thereof (such as an Fe or hinge Fe domain fragment), see, e.g., WO 98/23289; WO 97734631; and U.S. Pat. No. 6,277,375. Further, an antibody can be conjugated to albumin to make an antibody more stable in vivo or to have a longer half life in vivo. The techniques are known in the art, see e.g., WO 93/15199, WO 93/15200 and WO 01/77137: and EPO 413622. The antibody also can be modified, for example, by glycosylation, acetylation, phosphorylation, amidation, deri validation by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein and so on. Techniques for conjugating such a therapeutic moiety to antibodies are well known, see, e.g., Arnonetal., in Monoclonal Antibodies and Cancer Therapy. Reisfeld et al. (eds.), Alan R. liss (1985); HeUsttom et., in Controlled Drug Delivery, 2nd ed., Robinson et al., eds.. Marcel Dekkef (1987); Thorpe^ in MonocionaJ Antibodies '84; Biological And Clinical Applications, Pinchera et al, eds. (1985); Monoclonal Antibodies For Cancer Detection and Therapy, Baldwin et al., eds.. Academic Press (1985); and Thorpe et al., Immunoi Rev 62:119 (1982). Alternatively, an antibody can be conjugated to a second antibody to form an antibody beteroconjugate, such as a bifunctional antibody, see, e.g., U.S. Pat. No. 4,676,980. The conjugates of the invention can be used for modifying a given biological response, the therapeutic agent or drug moiety is not to be construed as limited to classical chemical therapeutic agents. For example, the drug moiety may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin or diphtheria toxin; a protein such as tumor necrosis factor, a-'mterreron, ^-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator, an apoptotic agent, e.g, TKF-a, TNF-p\ AIM I (WO 97/33899), AIM II (WO 97/34911), Fas ligand (Takahashi et al, bit Immunol, 6:1567 (1994)), VEGF (WO 99/23105); a thrombotic agent; an anti-angiogenic agent, e.g., angiostatin or endostatin; or biological response modifiers such as, for example, lymphokines. interleukin-I (IL-l), interieukin-2 (IL-2), imerleukin-6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (GCSF) or other growth factors. The antibody or variant composition will be formulated, dosed and administered in a manner consistent with good medicel practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical conditio'1 of the individual patient, the cause of the disorder, the site of delivery of the asgenf, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The "therapeutically effective amount" of the antibody orvariant to be administered will be governed by such considerations, and can be the minimum amount necessary to prevent, ameliorate or treat an extended Type I glycosphingolipid disease. condition or disorder. As used herein, the term "effective amount" refers to the amount of a therapy (e.g., a prophylactic or therapeutic agent), which is sufficient to reduce the severity and/or duration of an extended Type I glycosphingoHpid related or associated disease, ameliorate one or more symptoms thereof, prevent the advancement of an extended Type I glycosphingolipid related or associated disease or cause regression of an extended Type 1 glycosphingolipid related or associated disease, or which is sufficient to result in the prevention of the development, recurrence, onset, or progression of an extended Type .1 glycosphingolipid related or associated disease or one or more symptoms thereof, or enhance or improve the prophylactic and/or therapeutic eftect(s) of another therapy (e,g., another therapeutic agent) useful for treating an extended Type I glycosphingolipid disease related or associated . for example, a treatment of interest can reduce a symptom, based on baseline or a .norma! level, by at least about 5%, preferably at least 10%, at least 15%. at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at. least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100%. In one other embodiment, an effective amount of a therapeutic or a prophylactic agent reduces a symptom of an extended Type I glycosphingoliid related or associated disease, such as a cancer, by at least about 5%, preferablyp at least 10%, at least 15%, at least 20%: at least 25%, at least 30%, at. least 35%, a! least 40%, at least 45%, at at least 50%, at least 55%, at least The amount of therapeutic polypeptide, antibody or fragment thereof which will be effective in the use or treatment of a particular disorder or condition will depend on. the nature of the disorder or condition, and can be determined by standard clinical techniques. Where possible, a dose-response curve and the pharmaceutical compositions of the invention can be first derived in vitro. If a suitable animal model system is available, again a dose-response curve can be obtained and used to extrapolate a suitable human dose practicing methods known in the art. However, based on common knowledge of the art, a pharmaceutical composition effective in promoting a diminution of an inflammatory effect, for example, may provide a local therapeutic agent concentration of between about 5 and about 20 ng/ml, and, preferably, between about 10 and about 20 ug/ml In a preferred embodiment, an aqueous solution of therapeutic polypeptide, antibody or fragment thereof can be administered by subcutaneous injection. Each dose may range from about 0.5 mg to about 50 mg per kilogram of body weight, or more preferably, from about 3 mg to about 30 mg per kilogram body weight. The dosage can be ascertained empirically for the particular disease, patient population , mode of administration and so on, practicing pharmaceutic methods known hi the art. The dosing schedule for subcutaneous administration may vary from once a week to daily to multiple times a day depending on a number of clinical factors, including the type of disease, severity of disease and the sensitivity of the subject to the therapeutic agent. In one embodiment, the composition is formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous administration to humans. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the composition may also include a solubilizing agent and a local anesthetic such as lidocaine or other "caine" anesthetic to ease pain attire site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry iyophilized powder or a concentrate in a sealed container, such as an ampoule or sachet indicating the quantity of active agent. Where the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the composition is administered by injection., an ampoule of sterile water for injection or saline can be provided, for example, in a kit, so that the ingredients may be mixed prior to administration. The invention also provides that a liquid formulation of the present invention is packaged in a sealed container such as an ampule or sachet indicating the quantity of the product of interest. The liquid formulations of die instant invention can be in a sealed container Indicating the quantity and concentration of the antibody or antibody fragment. The liquid formulation of the instant invention can be supplied in a sealed container with at least about 15 mg/ml, 20 mg/ml, 30 mg/ml, 40 mg/ml, 50 trig/mi 60 mg/ml, 70 mg/ml, 80 mg/ml, 90 mg/ml, 100 mg/ml, ! 50 mg/ml 200 mg/ml. 250 mg/ml, or 300 mg/ml of extended Type-1 glycosphingolipid antibody in a quantity of about 1 ml, 2 nil, 3 mi, 4 ml, 5 ml 6 ml, 7 mi, 8 mi, 9 ml 1.0 ml, 15 ml or 20 ml, for example. An article of manufacture containing materials useful for the treatment of the disorders described above is provided. The article of manufacture comprises a container and a label. Suitable containers include, for example, bottles, vials, syringes and test tubes. The containers may be formed from a variety of materials such as glass or plastic. The container holds a composition which is effective for diagnosing, preventing or treating an extended Type 1 glycosphingolipid condition or disease and may have a sterile access port (for example, the container may be an intravenous solution bag or a vial having a stopper pierceable by a. hypodermic injection needle). The label on or associated with the container indicates that the composition is used for treating the condition of choice. The article of manufacture may further comprise a second container comprising a pharmaceutically acceptable buffer, such as phosphate-buffered saline. Ringer's solution and dextrose solution. It may further include, other materials desirable from a. commercial and user standpoint, including buffers, diluents, filters, needles, syringes and package inserts with instructions for use. In another aspect of the invention, nucleic acids comprising sequences encoding antibodies or functional derivatives thereof, are administered to treat, inhibit or prevent a disease or disorder associated with aberrant expression and/or activity of extended Type I glycosphmgoltpid, by way of gene therapy. Gene therapy refers to therapy performed by the administration to a subject of an expressed or expressible nucleic acid of interest. Alternatively, cells manipulated to carry gene sequences of interest are administered to a host. In an embodiment of the invention, the nucleic acids produce the encoded protein in and by target host cells that mediate a therapeutic effect. Any of the methods for gene therapy available can. be used according to the instant invention. For general reviews of the methods of gene therapy, see Goldspiel et aL Clinical Pharmacy .12:488 (1993); Wu et aL Biotherapy 3:87 (1991): Tolstoshev, Ann Rev Pharmacol Toxicol 32:573 (1993); Mulligan, Science 260:926 (1993); Morgan et al., Ann Rev Biochem 62:191 (1993); and May, T1BTECB 11:1.55 (1993). In one aspect, the compound comprises nucleic acid sequences encoding an antibody, or functional binding fragments thereof, said nucleic acid sequences being part of expression vectors that express the antibody or fragments or chimeric proteins or heavy or light chains thereof in a suitable host. In particular, such nucleic acid sequences have promoters operably linked to the antibody or antigen-binding coding region, said promoter being inducible or constitutive, and, optionally, tissue-specific, as well as other regulatory sequences. In another particular embodiment, nucleic acid molecules are used in which the antibody coding sequences and any other desired sequences are flanked by regions that promote homologous recombination at a desired site in the genome, thus providing for integration and imrachioniosomal expression of the antibody-encoding nucleic acids (Roller et al, Proc Natl Acad Sci USA 86:8932 (1989); Zijlstra et al., Nature 342:435 (1989)). In specific embodiments, the expressed antibody molecule is a single chain antibody; alternatively, the nucleic acid sequences include sequences encoding both the heavy and light chains, or fragments thereof, of the antibody. Alternative methods for integration include using particular transcription factors that recognize specific nucleic acid sequences, z.inc fingers and so on. Delivery of the micieic acids into a patient may be either direct, in which case the patient is directly exposed to the nucleic acid or nucleic acid-carrying vectors, or indirect, in which case, cells are first transformed with the nucleic acids in vitro, then transplanted into the patient. In one embodiment, the nucleic acid sequences are directly administered in vivo and are expressed to produce the encoded product. That can be accomplished by any of numerous methods known in the art, e.g., by constructing the antibody encoding sequences as part of an appropriate nucleic acid expression vector and administering same so that the vectors become intracellular, e.g., by infection using defective or attenuated retroviral or other viral vectors (see U.S. Pat. No. 4,980,286), by direct injection of naked DNA, by use of microparticfe bombardment (e.g., a gene gun; Bioltstic, Dupont), using non-viral vectors, such as synthetic compositions comprising an amphipathic compound thai binds the hydrophilic nucleic acid and has the ability to fuse with cells, generally thus containing a hydrophobic portion for combining with membranes, coating with lipids or cell-surface receptors or traiisfectiiig agents, encapsulation in liposomes, inicroparticles, or microcapsules, by administering the vector in linkage with a peptide which is known to enter the nucleus, by administering the vector in linkage with a ligand subject to receptor-mediated endocytosis (see, e.g., Wu et al., J Biol Chem 262:4429 (1987)) (which can be used to target ceil types specifically expressing the receptors) etc. In another embodiment, nucleic acid-ligand complexes can be formed in which the ligand comprises a fusogenic viral peptide to disrupt endosomes, allowing the nucleic acid to avoid lysosomal degradation. In yet another embodiment, the nucleic acid can be targeted in vivo for cell-specific uptake and expression, by targeting a specific receptor (see, e.g., WO 92/06180; WO 92/22635; WO92/20316; W093/14188 and WO 93/2022.1). Regarding vectors, for example, a lentiviral vector can be used as known in the art. The lenliviial vectors contain components for packaging the viral genome and integration into the host cell DNA. The nucleic acid sequences encoding the antibody to be used in gene therapy are cloned into one or more vectors, which Adenoviruses also may be used in the instant invention. Targets for adenoviais-based delivery systems include liver, the central nervous system, endothelial cells and muscle, for example. Adenoviruses infect non-dividing cells. an advantage over early retroviral vectors. Kozarsky et at, Curr Opin Gen Dev 3:499 (1993) present a review of adenovims-based gene therapy. Bout el al.t Human Gene Therapy 5:3 (1994) demonstrated the use of adenovirus vectors to transfer genes to the respiratory epitheiia of rhesus monkeys. Other instances of the use of adenoviruses in gene therapy can be found in Rosenfeld et at.. Science 252:431 (1991); Rosenfeld et al.. Cell 68:143 (1992); Mastrangeli et al., J Clin Invest 91:225 (1993); W094/12649; and Wang et al., Gene Therapy 2:775 {.1995). Adeno-associated virus (AAV) also can be used in gene therapy (Walsh et a!., Proc Soc Exp Biol Med 204:289 (1993); and U.S. Pat. Nos. 5,436,146; 6,632,670; and 6,642,051). Another approach to gene therapy involves transferring a gene to cells in tissue culture by methods such as electroporation, iipofec-tion. calcium phosphate-mediated transaction or viral infection. Usually, the method of transfer includes (lie transfer of a selectable marker to the cells. The cells then are placed under selection to isolate those cells that have taken up and are expressing iha transferred gene. Those cells then are delivered to a patient. Thus, the nucleic acid can be introduced into a cell prior to administration in vivo of the resulting recombinant cell. Sttch introduction can be carried out by any method known in the art, including but not limited to transfection, electroporation, microinjection, infection with a viral or bacteriophage vector containing the nucleic acid sequences, cell fusion, chromosome-mediated gene transfer, micro cell-mediated gene transfer, spheroplast fusion etc. Numerous techniques are blown in the art for the introduction of foreign genes into cells (see, e.g., Loeffler et a!., Meth Enzymol 217:599 (1 99.T); Cohen et af., SvJeih Enzymoi 217:618 (1993); and Cline, PharmTher 29:69 (1985)) and may be used in accordance with the present invention, provided that the necessary developmental and physiological functions of die recipient cells are not disrupted. The technique should provide for the stable transfer of the nucleic acid to the cell, so that the nucleic acid is expressed by the cell, heritable and expressed by the cell progeny, The resulting recombinant celts can be delivered to a patient by various methods known in the art. Recombinant blood cells (e.g., hematopoietic stem or progenitor cells) are preferably administered intravenously, for example, as known in the bone marrow transplantation art. The amount of cells envisioned for use depends on the desired effect, patient state etc., and can be determined by one skilled in the art Cells into which a nucleic acid can be introduced for purposes of gene therapy encompass any desired, available cell type, and include, but are not limited to, epithelial cells, endothelial cells, keratinocytes, fibroblasts, muscle cells, hepatocytes, blood cells, such as T lymphocytes, B lymphocytes, monocytes, macrophages, neutrophils, eosinophils, megakaryocytes and granulocytes, various stem or progenitor cells, in particular hematopoietic stem or progenitor celts, e.g., as obtained from bone marrow, umbilical cord blood, peripheral blood, fetal liver etc. In one embodiment, the cell used for gene therapy is autologous to the patient. Nucleic acid sequences encoding an antibody of the instant invention are introduced into die cells such that the trans gene is expressed by the celts or their progeny, and the recombinant cells then are administered in vivo for therapeutic effect. In a specific embodiment, stem or progenitor cells are used. Any stem and/or progenitor cells which can be isolated and maintained in vitro can potentially be used in accordance with the embodiment of the instant invention {see e.g., WO 94/08598; Stemple et a!.. Cell 71:973 (1992); Rheinwaki Meth Cell Bio 2 3 A:229 (1980); and Pitteikow et at., Mayo Clinic Proc 61:771 (1986)). Because extended TypeTglycosphingotipid is expressed on, for example, B cells, blood ceils and bone marrow cells are suitable host cells. However, the scope of the instant invention regarding the use of stem celt hosts does not contemplate the making and usimg of a transgenic to make a transgenic organism by administering the transgene of interest to embryos and/or embryonic stem cells. The invention thus provides methods of treatment, prophylaxis and amelioration of extended Type I glycosphmgohipid related and associated diseases or one or more symptoms thereof by administering to a subject an effective amount of, for example, a liquid formulation, an antibody or variant thereof of the invention. The subject is preferably a mammal such as non-primate (e.g., cows, pigs, horses, cats, dogs, rats etc.) and a primate (e.g., monkey, such as a cynomolgus monkey, and a human). In a preferred embodiment, the subject is a human. Extended Type I glycosphingoiipid also is expressed on certain cancer cells, such as pancreas, colon and bladder, as well as cm j cell leukemias (Qrnping et af., Oncogene 24:5T3-584,2005), antfsiimufation of extended Type I glycosphingoiipid correlated with proliferation of carcinoma cells, Meijer et aL Cane Res 66:9576-9582, 2006. Thus, the antibody or derivative thereof of interest can be nsed to control proliferation of cancer cells expressing extended Typs J glycosphingoiipid, which cancers are identified by determining presence of extended Type I glycosphingoiipid expression by a diagnostic assay taught herein. The antibody of interest can reduce infiltration of malignant cells, reduce resistance to aptoptosis and minimize proliferation. Such patients then are administered a cancer cell proliferation mhihhmg aitiount of an antibody, or derivative thereof of interest as provided herein. As taught herein, an antibody or antigen binding portion thereof can be administered to a patient, in a number of ways, including administering a polypeptide, a polynucleotide and so on. Essentially eny cancer that expresses a Type 1 epitope of interest can be detected and/or treaty with an antibody of interest. For example, the malignant cell can be an epithelial cell. The epithelial cell can be found in any malignant cell of any organ or tissue origin such as, colon, rectum, esophagus, lung, prostate, breast, pancreas, the oral cavity, vagina, the gastrointestinal tract in general, urinary tract and so on. However, the cancer need not be limited to an epithelial cell, so fong as the malignant cell expresses a Type 1 epitope of interest. The invention now will be exemplified for the benefit of the artisan by the following non-limiting examples that depict some of the embodiments by and in which the instant invention can be practiced. EXAMPLES EXAMPLE I: GENERATION OF IMMUNOGEN Coio205 cells (ATCC) (Semple el aL Cancer Res 38: 1345-1.355,1978) are grown in RPMI 1640 medium containing 10% fetal calf serum. Harvested cells are washed twice with PBS and stored at -20°C until needed. Cell pellets are extracted with isopropanol-hexane-water (H W) (55:25:20) followed by Folch partition, DEAE Sephadex. chromatography and. HPLC on an latrobead 6RS-801Q column. Gradient etution of the upper-phase neutral fraction is performed in IHW from 55:40:5 to 55:25.20 over 200 minutes. Fractions are collected and pooled according to HPTLC migration in ehlorofor.m-methanol-waier (50:40:10). The extended Type i. chain glycosphingolipids are purified further by preparative TLC on Merck HPTLC plates {Silica. Get 60, Merck, Darmstadt, Germany), see U.S. Pat No. 6,083,929. A positive band (by immune staining with mAb IMH2) which migrated just below dimeric he" antigen is purified as taught herein. f00293] The colorectal adenocarcinoma cells CoJo205 (ATCC CCL-222) and DLD-1 (ATCC CCL-221) are cultured in RPMI 1640 medium (Invitrogen Co.. Cat. No. 31800) supplemented with 1 mM sodium pyruvate (Invitrogen Co., Cat. No. 11.360). Other colorectal adenocarcinoma cells, SWf [ i.6 (ATCC CCL-233) and HT-29 (ATCCHTB-38), and lung-derived T84 ceils (ATCC, CCL-248) are separately maintained in Leibovitz's 1,-15 medium (Invitrogen Co., Cat. No. 41300), McCoy's 5a medium (Invitrogen Co., Cat. No. i 2330) and DMEM/'F 12 medium (Invitrogen Co., Cat. No. 12400). The KATO II] gastric carcinoma cells (ATCC HTB-103) are cultured in [MDM medium (Invitrogen Co., Cat. No. 12200). All media used in the studies are supplemented with 10% fetal calf serum. EXAMPLE 2: GENERATION OF AM If XI ENDED TYPE I GLYCOSPHINGO'LIFIB MABS KM mice (Kirin Brewery Co., Ltd.) are generated by cross breeding double transchromosomic mice and transgenic mice. KM '^ice possess human chromosome fragments containing the entire human immunoglobulin heavy chain loci and a YAC transgene for half of the human immuiwglobulin kappa light chain loci. KM mice are engineered to express neither endogenous immunoglobulin heavy chain nor kappa light chain. All of the animals are maintained and handled according to the rules and regulations accepted in the t,ft- Co3o205 ceils are injected intraperitoneatty into KM mice even' 3 weeks V!) x Y$ cftWsSSnjttYiOYi) Sot a tcfta\ oS *V mjectaoift, ioWtrw^V^ ^riwti t£ v£xtfot& Type I chain glycosphingohpids which are isolated from Colo205 cells and adsorbed on lipopolysaccharide (Sigma, L-7011) (Young et a!., i Exp. Med. 150:1008-1019, 1979) every week for 8 injections. The anti-Coio205 tieutral glycosphingolipid titers of inimuni/.ed mice are monitored by ELISA, using ami-human kappa-HRP (Southern Biotechnology Associates, Cat. No. 9220-05) as the secondary antibody until the titer reached 1:6000. Three days after die final injection, splenocytes from the boosted mouse are fused with P3/NS1/1 -Ag4- i (NS-1) mouse myeloma cells (ATCC TIB-18) practicing methods known in the art. Mybridomas are screened by ELISA using 96-well ELISA plates (Corstar, Cat. No. 2592) coated with Colo205 neutral giytolipid. Mouse anti-human IgG antibodies conjugated with HRP are used as the secondary antibody (Southern Biotechnology Associates. Cat. No, 9040-05) and terametltylbenzidene (1MB) (Kem.-Zn.-Tee Diagnostics, Cat. No. 4390) is used as the substrate. Hybridoma supernatants showing high reactivity with Colo205 neutral glycolipids are further confirmed by HPTLC jniniunostaining and by flow cytometry. Clones strongly staining the extended Type 1 chain glycolipids and showing high binding on the surface of Colo205 cells are repeatedly stibcloned by limiting dilution until stable clones are established. One stable clone is GNX-8. EXAMPLE 3; GNX-8 ANTIBODY Monoclonal antibody is purified from culture supernatants using protein A Sepharose (GE Healthcare 17-129-79-02) with pH gradient elution according to the manufacturer's suggested procedures. Each fraction is collected and the presence of antibody is examined by EL1SA. Fractions with Colo205 neutral glycolipid binding activity are pooled and dialyzed against PBS (pH 7.4), Purified antibodies are aliquot and stored at -20° C. Hie concentration of monoclonal antibody is determined with the Bio-Rad Protein Assay kit (Bio-Rad, Cat. No. 500-0006} using IgG as the standard according to the manufacturer's recommended procedures. The isotype of GNX-8 is determined using an ELISA. GNX-8 is a human IgGl and the light chain is kappa. Purified GNX-8 is applied to 10% SDS-polyacrylamide geis after being boiled in 2X SDS gel-loading buffer with (reducing condition) or without (non-reducing condition) pVmercaptoethanol. Electrophoresis is conducted using the Minutest-PROTEANS Electrophoresis System (BIO-RAD) according to the manufacturer's recommendations. GNX-8 separated on reducing SDS-PAGE gels is transferred onto nitrocellulose (NC) membranes (Amersham) and blocked with 3% skim milk in PBS. The membrane is incubated with secondary antibody for 1 hour at room temperature. MRP-labeled goat anti-human igG(y) antibody (Zymed, 62-8420) at 1:5000 dilution and HRP-labeled rabbit anti-human kappa chain IgG antibody (DAKO; P0129) at 1:2000 dilution are separately used to detect the heavy chain and light chain of GNX-8. Western Lightning ! Chemi luminescence Reagent Plus (PerkinElmer Life Sciences^ Cat. No. NEL105) is used to develop the signal on BioMax Light Film (KODAK, Cat. No. 1788207). Under reducing conditions, the molecular weight of die GNX-8 light chain and heavy chain are as expected for an IgG. GNX-8 is a human monoclonal antibody by Western blot with goat anti-human IgG(y)-HR.P and rabbit anti-human kappa chain-HRP as secondary antibodies, separately. GNX-8 is a human antibody by EIJSA isotyping. The pi analysis of GNX-8 is determined by the PhastSystem (Pharmacia). Briefly, an antibody sample and pi standard are applied on an 3EF PhastGel 3-9 using a PhastGel Sample applicator 8/1 comb and are separated according to the manufacturer's protocol. The gel subsequently is silver stained in the PhastSystem Development Unit (Pharmacia) according to the manufacturer's protocol. The pi analysis reveals multiple bands ranging from pH 8.15 to 8.65 indicating the possibility of post-trans Sational modifications of the antibody. The high pi indicates that GNX-8 will be soluble at physiologic pH. For detecting cell binding activity, 2 x 10" cells are washed with PBS and incubated with various concentrations of antibody for 30 minutes at room temperature. After a PBS wash, FITC-labeled goat anti-human IgG (Fc) antibodies at 1:3000 dilution (ICN. Cat no. 55198) are added to each cell sample for an additional 30 minutes at room temperature. For CDC studies, cells after antibody treatment are washed three times with PBS and incubated with 1 iii of propidium iodide solution (Sigma-Aldrich, P4846) for 30 minutes. After a final PBS washing, celts are analyzed on a flow cytometer {BD, FACSort). The results are processed with CELLQuesl3.3 (BD). EXAMPLE 4: CYTOTOXICITY ASSAY tinman colon cancer cell lines, SVV1116, Colo205 and DLD-1, are seeded in 48-well plates (Corning Costar) at a density of 2 x 104 ceils/well. After being cultured overnight, the cells are incubated in 500 u! of medium with 25% non-inactivated human serum at various antibody concentrations for 2 hr. After a PBS wash, the remaining live cells are quantified by propidium iodide (PI) solution (Sigma-Aldrich, P4846) staining and are analyzed by flow cytometry. Normal human IgGs purified from normal human serum axe used as a negative control. In an alternative assay, target cells are labeled by incubation with about 100 ul of 51Cr for about 90 min. at about 37O C. After washing (3x) and incubation (about I hr at 37° C), cells (about I x 106 ml) are suspended in RPMl-1640 supplemented with about 25 iriM HEPES buffer and about 3% bovine serum albumin. About 20 id of labeled cells, about 100 p.1 of mAb and 25% heat inactivated Iranian serum are mixed in the wells of microliter U bottom plates (Coming, N.Y.). Non-specific mouse Ig (Sigma, St. Louis, MO) can be used as a negative control. After about 4 hr incubation, the plates are cemrifuged (500 x g, 2 min) with a hanging plate holder assembled in a centrifuge, and radioactivity in about 100 u.1 supernatant in each well is measured with a gamma counter. Each experimental group can be tested in triplicate. Percent specific lysis can be calculated according to the formula ([A-B] x 100)/C, where A=cpm in lyscd experimental cells; B-^pm in unlysed target cells; and Ocpm in total target cells. Spontaneous release preferably should not exceed 15% of maximally releasable labeled radioactivity. ADC'C assays are performed by the lactate dehydrogenase (LDH) release assay (Promega, CytoTox 96* Non-Radioactive Cytotoxicity Assay) using hitman peripheral blood mononuclear cells (PBMC) as effector eel Is prepared from healthy-donors using Ficoii-Paque (GE, 7 i -7167-00). The assay quantitatively measures lactate dehydrogenase (LDH), a stable cytosolic enzyme thai is released on cell lysis. Released LDH in culture supernatant is measured with a 30 minute coupled enzymatic assay, which results in (he conversion of a telra/.olium sab. (INT) into a red formazan product. The amount of color formed is proportional to the number of lysed cells. Colo205 cells used as target cells are distributed into 96-well I) bottom plates (2 x. 104 cells/well) and are incubated with antibodies in the presence of the PBMC with various Ii/T ratios for 4 hours at 37° C, The LDH activity in the supernatant was measured by CytoTox 96* "Non-Radioactive Cytotoxicity Assay. The percent specific cytolysis is calculated according to the following formula'. % specific lysis = 100 x (E-SR -Si) / (M -Sr ) where E is the experimental release (activity in die supernatant from target cells incubated with antibody and effector cells). Su is the spontaneous release in the presence of effector cells (activity in the supernatant from effector cells with medium alone), ST is the spontaneous release of target cells (activity in the supernatant from target cells incubated with medium alone), and M is the maximum release of target cells (activity released from target ceils iysed with 9% Triton X-100). The in vitro antitumor activity of GNX-8 is evaluated ny CDC assay. Treatment of human colorectal cancer cells. SW11.16. Colo205 and DLD-1, with GNX-S in the presence of 25% human serum, results in substantial cell lysis in a dose dependent manner, The results indicate that GNX-8 kills target cells through complement-dependent cytolysis. The CDC effect on SW11! 6 and Colo205 cells in some experiments is stronger than that on DLD-1 cells. the viability of cells is inversely proportional proportion to the level of expression of GNX-8 antigen. The CDC effect of GNX-8 and levels of GNX-8 antigen expression on the three colorectal cancer lines demonstrate that cancer cells with higher GNX-8 antigen expression are more susceptible to cytotoxicity while those with lower GNX-8 antigen expression have higher viability. The results lead to the conclusion that the antitumor activity of GNX-8 can depend on the expression level of GNX-S antigen. Patients with high GNX-8 antigen expression on tumor cells might be treated with GNX-8 alone, while tumors expressing lower levels of GNX-8 antigen, may benefit from a combination therapy with one or more other cancer drugs in addition to GNX-8 antibody. ADCC activity of human peripheral blood mononuclear cells (PBMCj is evaluated against human colorectal cancer Colo205 in the presence of GNX-8. ADCC activity with IMH2 is used as the positive control and human IgG as the negative control. GNX-8 induces strong ADCC' activity against Colo205 cells. The cytotoxic effect is correlated positively with both F/T ratio and GNX-8 concentration. One hundred per cent cell lysis is observed at H/T of about 20/1. A maximal ADCC effect, and a trend observed for about 50% lysis as welt, is observed at about S ug/ml of GNX-8 and at about 50 ug/ml for IMH2, respectively. Control human !gG shows no cytotoxic effect regardless of E/T ratio or IgG concentration. The dose of GNX-8 to reach 50% lysis is less than 1/10 needed for IMH2. EXAMPLE 5: BIACORE AFFINITY ANALYSIS Type I glycosphingolipids are affixed to a chip. Then die mAb's are exposed to the chip for kinetic measurements and epitope sequence analysis surrounding the antibody-antigen binding reaction, following the manufacturer's recommendations (GE Healthcare, Pistcataway, NJ). EXAMPLE 6: IN VIVO ASSAY Antitumor activity of GNX-8 is evaluated in a Colo205 xenograft model. Coio205 cells are washed twice with PBS and reconstituted at a cell density of 5 x 10*7.100 ul in PBS. Female nude mice of age 6-8 weeks are inoculated s.c. with 100 ul of the Colo205 cell suspension in the flank region. Tumor sixes are measured three times a week with a vernier caliper and tumor weights (mg) are estimated as (width3 x length)/2. GNX-8 or normal human IgG is i.p. injected in tumor-bearing nude mice according to designed doses and schedules. To evaluate the in vivo antitumor efficacy of GNX-8, cancer cells (5 x 10° cells/mouse) are injected in nude mice and treated with either GNX-8 (treatment group, S mice/group) or norma! human IgG (control group, 7 mice/group) 24 hours after tumor inoculation. Five doses (300 p.g'mouse) at 24-hour intervals and subsequently four doses (600 [.ig/mouse) at 48-hour intervals are injected in both groups. Tumor growth is significantly inhibited in GNX-8-treated mice. The treatment group reaches a median tumor weight of T.-'C (Treatment/Control) of about 23% on day 11 and continues at that approximate level to the end of the study. A T/C measure of Half (4/8) of the mice in the GNX-8 treatment group achieve long term tumor-free survival over 50 days. On the other hand, tumor size of the control group animals continually increases during the study. A similar study is conducted in a Colo205 xenograft nude mice model. The first dose of GNX-8 is given at a tumor size of 80 to 100 mg. GNX-8 (treatment group) and normal human IgG {control group) are injected once (300 fig/mouse) daily for five days, and with two similar doses at days 17 and 21. Significant tumor inhibition also is observed in the treatment group, although the treatments are discontinued after only 5 doses. The median tumor weight of T/C (Treatment/Control) is lower than 42% after day 10 and through to the end of the study, To determine whether host effector function contributed to GNX-8 efficacy, SCID mice bearing Colo205 xenografts are treated with GNX-S or normal human IgG at GOO jig/mouse twice weekly for three weeks. Tumor size is measured twice every week until the tumor size reached 10% of the body weight, which is considered the endpoim of the study, Survivability is prolonged in the treatment group. To explorei the occurrence of the GNX-8 epitope on human colorectal cancers, several human colorectal cancer cell lines are analyzed. For example, the in vivo inhibition of OLD-1 by GNX-8 is significant. EXAMPLE 7: GNX-8 ANTIGEN For the analysis of cell glycoprotein, cultured cells are scraped from the T-75 flasks and washed twice with PBS; followed by lysis buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCL 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS and 1 mM PMSF). The lysates are passed through a 26 gauge needle several times to disperse any large aggregates. Protein concentration is determined by Protein Assay Kit (Bio-Rad). The tysaies containing the same amount of proteins are separated on a gel and analyzed by Western blot with GNX-8 as the primary antibody and mouse anti-human IgG (Fc) labeled with II.RP (Southern Biotechnology Associates, #9040-05} as the secondary antibody. Western Lightning™ Chemiluminescenee Reagent Plus (PerkinElmer Life Sciences, Cat. No. NEL105) is used to develop the signal on BioMax Light Film (KODAK, Cat. No. 1788207). Neutral glycolipids (2μl/sample) axe spotted on a HPTLC plate (Merck, 1.05642, silica gel 60 F254). and developed with a mobile phase containing chloroform;methanol:water at a ratio of 50:40:10 (V:V:V). For glyean staining of glycolipids, 0.2% orcinol (Sigma, 0-1S75) in 10% I^S04 is sprayed onto a HPTLC plate and incubated for 10 minutes ins1100C in an oven. For tmimmostaiuing, the HPTLC plate is first fixed with 0.5% pol.y(isobiUyl methacrylaie) (Aldrich, 18.1544) in chloroforro:hexane, 1:9 (V:V) for 45 seconds, followed by blocking for JO minutes in 3% BSA/PBS. The plates then are washed with PBS and incubated with the primary antibody at room temperature for 1 hr, followed by biottnylated secondary antibody at room temperature for .1 hr. An Avidin-Bioik Complex kit (Vector Laboratories, Burlingame, CA) is used to amplify signals from the secondary antibody. The plate is incubated at room temperature for 30 minutes, followed by color development with an Immunostaining HRP-1000 kit (Konica Minolta, 130990) according to the manufacturer's protocol. To a lyophiliix*d sample, 20 ul of 48% hydrogen fluoride (HP) (Merck) are added, and then the mixture is incubated at 4° C for 48 h. At the end of the reaction, HF is removed with N2 gas. The defttcosylaled glycolipids are used for specificity study of GNX-8. The neutral glycolipids of Coto205 are treated with HF and analyzed by MALD3-TOF MS to confirm Ihe removal of IVicose. TI..C imnrunostaiuing is performed to analyze the specificity of GNX-8 directed to Colo205 neutral glycolipids before and after HF treatment GNX-8 recognizes uncleaved glycolipids but not the defucosylated forms suggesting that, the epitope of GNX-8 is a carbohydrate moiety and fucose is an essential component of the structure. The specificity of GNX-8 is characterized further by HPTLC immiitiostaining on neutral and monosialyl glycolipids isolated from Colo205 cells. One hundred grams of Colo205 cells are collected, and glycolipid fractions are extracted. Co1o205 glycolipids separated by TLC are stained for carbohydrate with orcinai/H2S04. The positions of Lea ,Leb,Lea-Lea and Leb-Len are identified according to Stroud et al. (1992) supra. Sialyl Lea (SLeB) is indicated by staining with mAb NKH3 (U.S. Pat. No. 5,240,833) and was later identified with MAL.DI-MS. HPTLC immunostaining of the same glycolJpid fractions are conducted with CF4C4 (U.S. Pat. No. 5,011.920) (anti-Le8), T218 (Abeam, Cambridge, MA) (antJ-Leb), IMH2 (Stroud et ai., 1992, supra) (anii-Leb-Lea), and GNX-S antibodies. Hie results indicate that GNX-8 strongly reacts with extended Type I chain glycolipids. GNX-8 did not bind to Le" extended Type I chains. The monosialyl glycolipids of Colo205 cells are not recognized by GNX-S. GNX-S shows very slight cross-reactivity with Leb at higher concentration (0.6 p.g/mt). Unlike 1MH2, GNX-8 did not bind to Les or to Ley. GNX-8 binds to an extended chain containing Leb. GNX-8 binds to Le'-Lea. In addition to TLC immunostaining, the epitope of GNX-8 is characterized by competitive ELISA using synthetic gtycans Leb, Le"-Le\ Leb-Les and LeM-ex as inhibitors, and the Leb-Le:VLea-Le'J glycotipid mixture as a positive control The results indicate that GNX-8 slightly cross-reacts with Leb-Lex at high inhibitor concentration, but has no reactivity with other tested synthetic glycans including synthetic Lcb glycans. The binding activity of GNX-8 to extended Leb is 1000 times higher than that to simple Leb. Based on the results, the epitope of GNX-8 likely is an Leb structure on an extended Type I chain with fucosylation, but it is not a simple Leb EXAMPLE 8: CELL AND TISSUE DISTRIBUTION Formalin-fixed paraffin-embedded specimens of human normal and cancer tissues are obtained, for example, from US Biomax. The formalin-fixed, paraffin-embedded tissue arrays of norma) and malignant human tissues are blocked with 0.1 % skim milk in PBS for 30 minutes. After an additional 10 minutes incubation with 3% H:02, the tissue arrays are washed thrice with PBS before samples are incubated with 0.1% BSA/PBS-diluted biotinylated GNX-8 for 1 hour. Then the tissue samples are reacted with biotin-streptavidin-peroxidase complex (ABC kit, Vector, #PK-6100) for 30 minutes for signal amplification. The DAB PLUS Substrate Kit (Zymed #00-2020,) is used to visualize immunoreactive staining according to the manufacturer's protocol. Counterstaming is performed using hematoxylin. The results are determined by visualization under a light microscope. The expression of GNX-8 antigen on human cancer cells is evaluated hy flow cytometry. A number of human colorectal and gastric tumor eel! lines, such as, Colo205, ITT-29, DLD-L SWI! 16, T84 and KATO HI, are separately examined for the expression of GNX-8 antigen by flow cytometry. Flow cytometric analyses demonstrate that GNX-8 exhibits binding activity to all tested cancer cell lines. However, the binding is significantly stronger to SWI 116, Colo205 and Dl.D-1 cells than to the other tested human cancer cell lines. hi addition, GNX-8 antigen expression is tested on HL60 (a promyelocyte ceil line), MCF-7 (a breast cancer ceil line) and PANC-1 (a pancreas cancer cell line), as well as on a mouse colon cancer ceil line, CT26. GNX-8 does not bind to those four cell lines. Two colorectal cancer eel! lines, Colo'205 and SWI i 16, are analyzed by Western blot. The two cell lines demonstrated strong binding with GNX-8 in flow cytometry analyses. The results show presence of GNX-8 antigen on glycoprotein of Colo205 and SWI {16 over a molecular weight range from 32 to > 3 75 kDa. Accordingly, GNX-8 antigens are not only in glycoHpids but also in glycoproteins. A variety of specimens from various organs, including both normal tissues and cancer tissues, are separately stained with GNX-S. Staining patterns in tissue specimens are evaluated by staining intensity and frequency of positive cells. Staining is graded on a scale of 1-r- \ 10-20%), 2+ (20-50%) or 3* (> 50%), whereas frequency is classified based on the percentage of positive ceils in each section. A strong correlation is observed between GNX-8 antigen expression in primary and metastatic colorectal carcinomas. Art immunohistochemical staining of a panel of tissue sections from a colorectal cancer patient is conducted. GNX-8 antigen is expressed not only on colorectal cancer tissues but also on adjacent tissues. For example, a polyp next to a cancer region is stained by GNX-S. However, no staining is observed on distal normal tissues. Hence, it can be concluded GNX-8 identifies transformed cells or cells undergoing transformation before recognizable cell morphology changes occur. GNX-8 antigen expression is also studied on various grades of cancer. GNX-S antigen is expressed in each cancer stage. GNX-8 does not bind to normal colon, rectum, stomach, small intestine, liver, esophagus, lung, prostate or breast. Fifty-eight percent (44/76) of colon cancer samples are stained with GNX-8; 47% of rectum cancer samples; 57% of metastatic colon cancer samples; 53% of stomach cancer samples; 29% of esophageal cancer samples; 22% of lung cancer samples; 4% of prostate cancer samples; 17% of breast cancer samples; and 67% of pancreatic samples are stained with GNX-8. GNX-8 does not bind to small intestine, liver and. kidney cancer samples. 'Table I Specificity of GNX-8 on Human Normal Tissues Normal Tissues Human tissues Incidence (No. positive/Na tested) Coion 14/102 Esophagus 314* Breast 13/56* Pancreas 4/12* Kidney 11/63* Rccttiro 1/106 Small intestine 0/2 Liver 0/4 Long on Prostate a/6 * stained on keralinizaUom of stratified squamous epithelium § stained on epithelial cells of duct systenviactiferoos ducts # stained on epithelial cells of duct system Tabic 2 Specificity of GNX-8 on Human Cancer Tissues Human cancer tissues incidence (No. positive/No, tested) Staining intensity and location Colon 44/76 >K5),2+(12), I-K27) Rectum 50/107 3-Kl?),2-K20), I-K17) Small intcslinc 0/10 Liver 0/12 Kidney O/'A Colon (metastatic) 27/47 2-K9X1+08) Esophagus 4/14 2-KI). HO) Lung 10/45 3-r(t), 2+{5), l-s-r'4) Prostate im 2t Breast 7/45 3-*"!).2*(4), 1-K2) Pancreas 8/12 2~0), l+(5) EXAMPLE 9: CLONING AND SEQUENCING OF GNX-8 GNX-8 producing hybridoma celts are routinely cultured in 1MDM (Invitrogen) containing 10% low IgG fetal bovine serum (HyClone), To prepare RNA tor cDNA synthesis, 1 x l06 hybridoma cells are first harvested by low speed centri&gation (1000 rpm, 5 rain). Total RJ^ A then is isolated from the cell pellet using TR120L reagent (invitrogen) according to the manufacturer's protocol. First strand cDNAs are synthesized from the purified RNA sample using the SMART RACE cDNA Amplification Kit (BD Biosoiences-Ctoniech). Briefly, 1 jig total RNA is incubated with 1 ul 5'-CDS and I pi SMART IIA oligo pritners at 70° C for 2 minutes. After addition of 2 id 5x. first-strand buffer, 1 id 20 mM DTT( I pA 10 mM dNTP and 1 {.d of PowerScript RT are added to the RNA/primer mixture. The sample is incubated further at 42° C for 1.5 hours. The first strand cDNA synthesis reaction is terminated by adding 100 p.! Tricine buffer and incubated at 72° C for 7 minutes. The cDNA encoding the heavy chain fragment of GNX-8 is amplified by PCR using UPM (BD SMART RACE cDNA Amplication Kit) and a primer of the 3' end of the heavy chain, CM, SEQ ID NO:3. The PCR reaction is carried out at 94" C for 30 seconds, followed by 58° C for 30 seconds, 72u C for 3 minutes, and that cycle is repeated 26 times. The variable region of the heavy chain cDNA is re-amplified from 1 j.tl of the above reaction product in the presence of NOP (SMART RACE amplification kit) and a primer of the middle of the heavy chain CH1, SEQ ID NO:4. The PCR reaction is performed at 94" C for 15 seconds, 68° C for 30 seconds and that cycle is repeated 25 times. The amplified product is purified using a PCR purification kit (GeneMark) and the nucleotide sequence is determined using a primer of the 5: end of the heavy chain CH 1, SEQ ID NO:5. Based on the sequence information, the full length heavy chain cDNA is specifically amplified by PCR from previously prepared first strand c-DNAs with newly synthesized primers, SEQ ID NO:6, and for the end of the heavy* chain gene, SEQ ID NO-.7, with the BD Advantage™ 2 PCR Enzyme System ("BD Biosciences). The PCR reaction is set at 94" C for 40 seconds, 60° C for 30 seconds and 72° C for 100 seconds, and that cycle is repeated 35 times. Hie amplified full length heavy chain cDNA is first double digested with EcoRI and Xbal. After gel purification, the recovered heavy chain cDNA then is ligated into the pClneo vector (Promega) at the same sites to obtain the expression vector pCl-GMX-8.H3. The inserted cDNA sequence is confirmed using a primer that.hybridizes upstream of the multiple cloning site, SEQ ID NO:8, and a primer downstream of the multiple cloning site, SEQ ID NO;*). GN.X-S heavy chai cDNA and the deduced amino acid sequence are shown in Table 3 as SEQ ID NGSn; 14 and 15, respectively. To identify the light chain cDN A sequences, the light chain peptide of GNX-8 is subjected to mass spectrometry analysis and database search. According to the protein identification information, the light chaintt of GNX-8 is homologous to the mouse X chain. A primer flanking the 5. end of mouse lambda gene constant region, SEQ ID NO:1 0, is synthesized. A cDNA including the variable region and a part of the constant region of the light chain gene is amplified from the first strand cDNAs described previously by touchdown PCR. The PCR reaction is carried out first for 5 cycles of 30 seconds at 94° C, 90 seconds at 72" C, followed by 5 cycles of 30 seconds at 94" C, 30 seconds at 66" C, 90 seconds at72"C and then the cycle of 30 seconds at 94° Ct 30 seconds at 63" C, and 90 seconds at 72s C is repeated 27 times. The amplified PCR fragments then are introduced into the yT&A vector (Yeastera Biotech) for positive clone identification. Four clones widi the expected size are selected for sequence determination with primer, SEQ ID NO:11. The results indicate that all fom clones have the identical cDNA with a structure homologous to the 5' end of known light chain genes. To reconstitute the full length light chain cDNA, a new set of primers, SEQ ID N0..12 and SEQ ID NO:13, are synthesized and the cDNA described above is used to prepare only the variable region of the light chain gene by PCR. 'Hie PCR reaction includes 30 cycles at 94* C for 30 seconds, 60" C for 30 seconds and 72" C for 1 minute. The amplified light chain variable region cDNA with incorporated EcoRI and BsiWI restriction enzyme sites is digested with the respective enzymes. After agarose gel purification, the amplified variable region cDNA fragment is Ugated into the same sites of the pCIck vector (a pClneo based expression vector with the insertion of a human K constant region at the Xbal and Not! sites) to give the light chain expression vector pCIck-GNX-8.mX. Sequencing confirmation is performed and the deduced nucleotide, as well as amino acid sequences of GNX-8 light chain are shown as SEQ ID NOS:1.6 and 17; respectively. A single vector that expresses both heavy chain and light chain genes of the recombinant GNX-S antibody is constructed with either the neomycin gene (pCkk-GNX-8 neo) or the DHFR gene (pCkk-GNX-8 DHFR) as a selection marker. The light chain vector pCIck-GNX-S.mA is linearized with BgHI followed by 5 v end deptiosphorylation xvith calf intestine phosphatase (CI P). The heavy chain vector pCI-GNX-8.H3 is cleaved with Bglll and NgoMlV. The BgUI-NgoMIV fragment containing the CMV promoter, full length heavy chain cDNA and SV40 polyA is recovered by gel extraction and introduced into the linearised light chain vector by blunt end ligation to form pCck.-GNX-S neo. Subsequently, the pCIck-GNX-S DHFR vector is generated by removing the neomycin gene with NgoMlV/Clal cleavage from pCkk-GNX-8 neo and replacement with the DHFR gene. The DHFR mini gene is cleaved from the pdbfr3.2 vector (ATCC No. 37166) by H.indl.ll/Sall digestion, and is separated and recovered by gel extraction. Both fragments are treated with Klenow to give blunt ends, then the DHFR gene is Ugated into the NgoMl V/Cial-cleaved pClck-GNX-8 neo fragment by blunt end ligation. Sequence (5o to 3') SE ELLGG 1 M1SRX 2 GCA TGT ACT AGT TTT GTC ACA AGA TTT GGG 3 GTG CAC GCC GCT GOT CAG GGC GCC TG 4 GGT GCC AGG GGG AAG ACC GATGG 5 CGA ATT CAC CAT GGC TGT CTC CTTCCTC 6 GCT CTA GAT CAT TTA CCC GGA GAC AGG 7 ACT CCC AGT TCA ATT ACA GC 8 TGG TIT GTC CAA ACT CAT C 9 GCA TGT ACT AGT TTT GTC ACA AGA TTT GGG 10 GTT TTC CCA GTC ACG AC 11 GCG AAT TCA CCA TGG CCT GGA err CAC 12 GCC GTA CGT AGG ACA GTG ACC TTG GTT C 13 GDSVSSKSVA IS GGGGAC AGTGTC TC TAGCAA GAGTGTTGCT 19 TYYRSKWYN 20 ACATACTACAGGTCCAAGT GGTATAAT 21 ARNFDY -i*i GCAACAAACTTTGACTAC 23 TGAVTTNNY 24 ACTGGGGCTGTTACAACT AATAACTAT 25 ATS 26 GCTACCAGC 27 ALWYNTHFV 2S GCTCTATGG1ACAACACCC ATTTTGTT 29 SEQIDNO:14 Length: 318 Type: DNA (heavy chain, variable region) GGACTGGTGAAGCCCTCGCAGACCCTCTCACTCACCTGTGCCATCTCCGG GGACAGTGTCTCTAGCAAGAGTGTTGCTTGGAACTGGATCAGGCAGTCC CCA'rTGAGAGGCCTTGAGTGGCTGGGAAGGACATAC TACAGG1'CCAAGT GGTATAATGAATATGCAGTATCTGTGAAAAGTCGAATAACCATCAATCC AGACACATCCAAGAACCAGTTCTCGCTGCACCTGAACTCTGTGACTCCCG AGGACACGGCTGTCTATTACTGTGCAAGAAACTTTGACTACTGCK3GCCA GGGAACCCTGGTCACCGTCTCC SEQ ID NO:lS Length: 106 Type: amino acid (heavy chain, variable region) GLVKPSQTLSLTCAISGDSVSSKSVAWNWIRQSPLRGLEWLGRTYYRSKWY NEYAVSVKSRrnNPDTSKNQFSLHLNSVIPEDTAVYYCARNFDYWGQGTL VTVS SEQ ID NO: 16 Length: 300 Type: DNA (light chain, variable region) CTCACCACAGCACCTGGTGGAAC;A(rrGATACTC;ACTTGTCGCTCAAGTAC TGGGGCTGTTACAACTAATAACTATGCCAACTGGGTCCAAGAAAAACCA GATCA'nTA'ITCACTGGTCTAATAGATGCrACCAGCAACCGAG'n'CCAGG KrrrCCTGTCAGATl'CTCCGCKrrCCXTGA'rTGGAGACAAGGCTGCCCTCA CCATCACAGGGGGACAGACTGAGGATGATGCAATGTATTTCTGTGCTCT ATGGTACAACACCCATTTTGTTTTCGGCGGTGGAACCAAGGTCACTGTCC TA SEQlDNO:l7 Length: 100 Type: amino acid (light chain, variable region) LTTAPGGTVILTCRSSTGAVTTNfNYANWVQEKPDHLFTGLIDATSNRVPGVP VRFSGSLIGDKAALTITGAQTEDDAMYFCALWYNTHFY'F'GGGTKVTVL Once the light and heavy chains are sequenced, the nucleic acids can be recoded to optimize expression in, for example, specific human host ceils. EXAMPLE 10: TRANSFECTOMAS NSO celis are grown to a density of 1 x 10*1 cells/ml. The cells are maintained in. exponential growth phase and medium is changed the day before transfection. The day of transfection, 40 K 10" cells are washed. Then, 10 p.g of linearized nucleic acid containing, for example, light chain DMA and linearized heavy chain DNA are added to the ceil suspension (the total DNA volume should be less than 50 ul) and the culture incubated on ice for 15 rain. The DNA and cell mixture is transferred to a chilled cuvette (0.4 cm) and an electric pulse (750 V and 25 uF) is applied. The cuvette is placed on ice immediately after the electric puise and kept on ice for 10-15 mm. The cells are collected and plated. The cells are incubated in a 5% CO? incubator for 12-16 days or until colonies appear. The supernatant of the cell colonies or cells grown in suspension culture is tested by EL1SA and positive transfectomas are cloned in fresh medium. To further screen the positive transfectomas, either titration ELIS A or the Biacore assay is conducted. Expanded tiansfectomas are maintained in shaker flasks and antibody or derivative thereof collected from the supernatant. EXAMPLE 11: PHARMACOKINETICS Rats are randomized into two groups (four rats/group). Animals receive 1 or 10 mg/kg of GNX-8 as a single i.v. bolus injection via a tail vein. Blood samples are collected at 0, 5, IS and 30 minutes, and L 2, 4,6. 24. 30, 72, 144,168, 216, 240, 312, 336 and 360 hours. Sernm is harvested and is stored ai -20° C until die GNX-8 concentration assay. GNX-8 concentration is determined by EL'ISA. GNX-8 is radiolabeled with '"I using the lODO-Gen method. Nude mice are used for in vivo biodistribution and imaging studies. Five million Co!o205 cells arc inoculated snbcutaneously. When the tumor reaches a size of 0.5 g. the biodistribution study is performed. For the biodistriborion study, mice are injected in the tail vein with 10 pCi/2.3 pg '■" !rlabeled GNX-8. Five mice are sacrificed at 6, 24,48, 72 and 96 hours after injection. Blood samples are taken just before the mice are sacrificed. Tumors and organs (brain, skin, muscle, bone, heart. lung, pancreas, eye, adrenal, tail, spleen, kidney, liver, bladder, stomach, small intestine and large intestine) are removed immediately and weighed. Presence of radiolabeled antibody in tumor, organ and "blood are separately counted in a v counter (Packard). Standards are counted each time with the tissues and tumors. Tissue radioactivities are expressed as the percentage of injected dose per gram of organ (YolD/g), Imaging studies are performed on a microSPECT single photon emission computerized tomography X-SPECT animal imaging system (Gamma Medica Inc. USA) and microCT X-ray computerized tomography. Nude mice bearing Colo205 tumors are i.v.-injected with 200 mCi/5.5mg/100ml ,3'l-labeled GNX-8 via tail vein. Images are acquired at 1. 6, 24. 48, 72 and 96 hours. Pharmacokinetic (PK.) studies are conducted for GNX-8 in rats, SCI.D mice and nude mice following a single i.v. administration. Serum concentration of GNX-8 is analyzed by ELIS A. A two-compartment model provides a good lit to tire data and generates the PK. parameters summarized in Tables 4 and 5. A dose-related increase in Cmax is observed following a single i.v, administration of 1.0 and 10 mg/kg GNX-8 in rats. GNX-8 is cleared from the serum in a terminal half-life of 3.8! and 4,98 days at a dose of 1 and 10 mg/kg, respectively. The pharmacokinelic parameters of GNX-8 after administration in nude mice and SCTD mice with or without Colo205 tumor-bearing mice presented with a T1/2 that is about one day in both species with tumor. For non-tumor-bearing animals. Tt; values are 58.09 hr in SOD mice and 98.31. hr in nude mice, respectively. From the pharmacokinetic parameters, the T1/2 is much longer in the non-tumor-bearing mice than in tumor-bearing mice. Table 4 Pharmacokinetic parameters in rats Parameter 1 mg/kg i.v. 10 rag/kg iv. Tmax (minutes) 5 5 Cmax(ug/ml) 9.49 102.08 T1/2 terminal (day) 3.81 4.98 Table 5 Pharmacokinetic parameters in SOD mice and Nude mice (i.v. administration of 5 rag/kg GiVX-8) SC1D mice Hude mice Tumor-bearing 4- - + - Cm* (tig/ml) 76.45 72.52 76.5 84.4 THUS (mill) 5 5 5 30 T].;; (elimination) (hr) 22.99 58.09 26.73 98.31 Biodistribution studies are done in nude mice bearing Cok>205 xenografts lo assess the in vivo tumor targeting activity and specificity of GNX-S. The highest level of !,1I-GNX-8 radioactivity is detected in plasma at all time points, 6 h , 24 h, 48 h, 72 h and 96 h. At 6 h, about 60% of the injected does per grain (%ID/g) is detected in plasma. At 48, 72 and 96 hours, the %lD/g for plasma was about 20%. The plasma level is significantly higher than in other organs, brain, skin, muscle, bone, heart, lung, pancreas, eye, adrenal gland, tail, spleen, kidney. liver, bladder, stomach, small intestine and large intestine, where the %ID/g at all time points in alt organs does not exceed 5%lD/g.. Radioactivity decreases over time hi plasma and in the other organs, except the tumor. Plasma radioactivity decreases by about 70% between 6 and 96 hours. Radioactivity of the tumor is initially higher than in normal organs. The highest tumor uptake is observed at 48 hours after13]I-GNX-8 injection, and maintains a steady state while the radioactivity of other organs decreases. Therefore, the tumor/organ ratios increase in other organs. Rapidly decreasing radioactivity is observed in plasma, heart, lung, adrenal gland, tail, spleen, kidney and liver between 6 and 24 hours. On the other hand, tumor/plasma ratios increase about 4 times from 6 to 96 hours after injection. No accumulation of 1Ml-GN'X-8 in kidney is observed. 'Oie in vivo tumor targeting activity in Colo205 tumor bearing nude mice is studied by imaging analysis. A time course experiment is done to monitor the distribution of 131I-GNX-8. The result also indicates that the majority of mI-GNX-8 is located in biood, and rumor targeting is cfearfy visible from 24 to 72 hours after injection. The in vivo data indicate that most GNX-8 is retained in blood after injection. There is no significant non-specific binding in various normal organs. Moreover, GNX-8 targets the €o!o205 tumor rapidly after i.v. injection and maintains labeling at a steady stare level over 96 hours. EXAMPLE 12: TOXICITY Single dose toxicity is performed in male and female BALB/c AnN Cri BR. mice (6 mice/group) at 8-9 weeks of age. Mice are i.v. injected with GNX-8 at a dose of 150 mg/kg or with vehicle alone (PBS). Body weight for all mice is measured on study days 1, S and 16 prior to sacrifice. Mice are observed daily for signs of morbidity or mortality. Repeat dose toxicity is carried out in male Sprague-Dawley Crl CD (SD) rats (6 rats/group) at 8 weeks of age. Each group is administered vehicle (PBS) or 3, 15 or 75 mg/kg/dose of GNX-8 twice weekly for 4 weeks. All animals are checked daily for mortality and any finding is recorded individually. Rats are weighed weekly during the pretreannent and treatment periods, and a final overnight lasting body weight is obtained at terminal sacrifice. Blood samples are collected at terminal sacrifice and evaluated for hematology and clinical chemistry parameters. The significance of differences in body weight and ail tested parameters is determined by Student's t test. To determine die cross reactivity of GNX-8 on normal human tissues, a very high dose (150 jig/ml) of biotinylated GNX-8 is used. A tissue array with 72 human tissues (24 types of normal organs taken from 3 normal hitman individuals) (US Biomax FDA 801-1) are stained with GNX-8. Based on the results from the Craan of the pharmacokinetic- study, GNX-8 is used at 150 ug/ml to ensure that GNX-8 at Cmw would have no serious cross reactivity with normal human tissues. That concentration ts much higher than regularly used in immunohistochernical studies. Weak to moderate staining of GNK-9 is observed on severaf human tissues of epithelial origin, including- mucosal epithelium of the gastrointestinal tract, epithelium cells of lactiferous ducts and keratinized cells of stratified squamous epithelium. According to the previous findings of Fmstad et al. (Clin. Cancer Res., 3:1433-1442,1997), antibodies introduced into circulating blood show specific-localization to carcinoma cells and did not accumulate in the antigen-positive, adjacent normal epithelial ceils. Also, antibodies do not traverse the basement membrane, Therefore, the staining in epithelial cells of ducts in normal tissue by GNX-S is not considered a detriment. Two additional studies are conducted for examining the cross reactivity of GNX-8 on normal human blood cells. All tested blood cells from the four various blood type (ABO) donors show negative response with GN.X-8. The results support that GNX-8 does not bind to blood cells. Therefore. GNX-8 administered to the circulator.' system should not cause damage to blood cells. To address the safety of GNX-8 in vivo, Wo studies are conducted to determine the acute and subacute toxicity effects. Tlie single dose toxicity of GNX-8 is tested in B ALB/c mice at a dose of ISO mg/kg. Mice are observed once daily and no deaths are found before scheduled sacrifice. All mice gain weight over the duration of the study and. there are no significant differences in mean body weight gain between the GNX-8 treatment group and the control group. 'Hie repeat dose toxicity of GNX-8 is performed in Sprague Dawiey Crl CD rats. Six animals of S weeks age are allocated to the groups. One group is administered vehicle (PBS) twice weekly for four weeks. Groups 2, 3 and 4 receive GNX-S in PBS at 3,15 and 75 mg/kg/dose, respectively, twice weekly for four weeks. All animals are examined daily for mortality and all findings are recorded. Ilats are weighed weekly during the preireatment and treatment periods and a final overnight fasting body weight is obtained at terminal sacrifice. Blood samples are collected at sacrifice and evaluated for hematology and clinical chemistry parameters. Significance of differences in body weight and all other measured parameters are analyzed by Student's t test. There are no clinical signs of toxicity related to GNX-S treatment. Analysis of final body weight gain indicates no difference between treatment and control groups. Blood samples of the control group and die high dose group are taken prior to euthanasia following an overnight fast, and are analyzed for hematology and clinical chemistry profiles. There are no statistically significant differences between the high dose and the control groups for hemoglobin amount, hematocrit, RBC number, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The results indicate no hematology toxicity is induced by repeated high-dose GNX-8 administration. For clinical chemistry analyses, mean values for the parameters for the control and the high-dose groups are indicated in Table 6. A statistically significant increase in total protein is noted in the high dose group thai might result from the repeated injections of high dose antibody. Additionally, a slight increase in albumin also is observed. However, the value is still within the range of normal limits for rats. The clinical chemistry data show no notable injury to metabolism and excretion function after repeated injection of high dose GJNX-8. [00383] Both hematology and clinical chemistry analyses verify the safery of repeated high dose GNX-8 administration over a four-week duration. Table 6 Clinical Chemistry Analyses Items Control High dose Mean SD mean SD albumin (g/dl) 3.3 0.4 3.9 0.2 ALT(GPT) (U/L) 118.6 50.0 67.6 6.0 AST(GOT) (U/L) 372.0 203.8 323.3 118.2 total bilirubin (mg/dl) 0.3 0.1 0.6 0.2 BUN (mg/dt) 12.3 5.8 11.2 1.5 Ca (mg/dl) 11.0 0.2 11.2 0.2 CI" (mmol/L) 108.0 2.1 106.0 2.2 cholesterol (mg/d!) 96.6 9.2 86.4 18.7 creatinine (mg/dl) 1.2 0.7 1.1 0.5 K (raraol/L) 4,9 0.6 4.9 0.5 Na* (mmol/L) 144.6 2.7 HS.2 4.2 phosphorous (mg/dl) 8.4 0.6 7.4 0.9 Total protein (g/di) 6.3 0.3 7.! 0.2 EXAMPLE 13: SCALE-UP To obtain a stable cell line for large scale production of GNX-8, NSO and CHO cell lines expressing recombinant GNX-8 (rGNX-8) are obtained. Briefly, c-DNAs encoding both the heavy and light chains of GNX.-8 are cloned from die original hybridoma. The isolated antibody genes then are reassembled in expression vectors. The molecular weight of rGNX-8 purified from media conditioned by transfected NSO cells is confirmed by SDS-PAGE. The specificity, binding activity and efficacy of rGNX-8 and the original GNX-8 hybridoma are compared by HPTLC, imraunostaining, flow cytometry and CDC assay. There are no differences between the original and recombinant GNX.-8 antibodies. [00386] The N-gtycosylation profiles of rGNX-8 and GNX-8 then are analyzed by MALDI-MS. The data illustrate a highly similar N-linked sugar pattern between the two antibodies. Almost ail N-glycans of the two antibodies contain the core rucosylatioii structure, but no tenninal sialic acids. Dihydrofolate reductase deficient Chinese hamster ovary {CH07dh.fr*) cells (ATCC CRL-9096) are maintained in IMDM containing 5% FBS and supplemented with 100 nM hypoxanthine and 16 uM thymidine. To prepare recombinant GNX-8 production ceil lines, expression vector pClck-GNX-8 DHFR is linearized by BamTil and the concentration of recovered ON A in solution is determined by Od260 absorbance. Approximately 1.2 x 106 CHO/dhfr* cells are transfected with 10 μg linearized DNA and 30 pi of Fngeneti transfection reagent (Roche) according to the manufacturer's instructions. After 48 hours, the culture medium, is replaced with 5% dialyzed fetal bovine serum containing IMDM for transfectant selection. The selection is continued for approximately two weeks until stable colonies are obtained. Multiple colonies are picked and cultured under the same selective medium in 48-welt plates. Individual CHO clones are screened for rGNX-8 expression by antigen-specific ELISA using HRP-iabded anti-human IgG(Fc) antibodies as the second antibody. A CHO clone that expressed high levels of antibody is selected for subsequent gene amplification with methotrexate (MTX). Gerte amplification in tO «M of MTX results in more than a 30-fold increase of rGNX-8 secretion. The stable CHO clone is named CHO-rGNX-8.5M10. CHO-rGNX-8.5M10 cells are later adapted to serum-free culture in shaking flasks and achieve a maximum yield of approximately 120 p-g/ml of GNX-8 over a 14-day culture. The culture supernatant is collected and purified by Protein A chromatography. The rGNX-8 antibody purified from the CHO culture supernatant by Protein A chromatography reveals the expected light chain and heavy chain peptide bands on SDS-PAGE. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims. WE CLAIM : 1. A human monoclonal antibody or antigen binding portion thereof that specifically binds an epitope comprising an extended Type I chain comprising Le „ wherein said epitope is expressed on a cancer cell, wherein said antibody or antigen binding portion thereof does not bind to human erythrocytes. 2. The antibody of claim 1, which does not bind to Le*. 3. The antibody of claim 1, which does not bind to Ley. 4. The antibody of claim 1 „ which does not bind to Ler-Le5. The antibody of claim 1, which lyses about 50% of Co!o205 cells in an ADCC assay at an E/T ratio of about 20/1 at an antibody concentration of about 5 ug/mt. 6. The antibody of claim I, wherein said cancer cell expresses Leh-Le". 7. The antibody of claim 1, wherein said cancer cell is an epithelial cell. 8. The antibody of claim 1, wherein said epithelial eel! comprises colon, rectum, esophagus, lung, prostate, breast or pancreas. 9. The antibody of claim 1, wherein said portion thereof is an scf,. 10. The antibody of claim I, comprising a K. chain. 11. The antibody of claim I. comprising a y chain. 12. The antibody of claim 1, comprising a CDR region obtained from GNX-8. 13. A composition comprising the antibody of claim I and a pharmacologically active agent. 14. An article of manufacture comprising the antibody of claim 1 and a detectable moiety. 15. A composition comprising the antibody of claim I and a phamutceuttcaHy acceptable carrier, excipient or diluent.

Documents:

376-mumnp-2011-abstract.pdf

376-mumnp-2011-assignment.pdf

376-mumnp-2011-claims.pdf

376-MUMNP-2011-CORRESPONDENCE(2-5-2014).pdf

376-MUMNP-2011-CORRESPONDENCE(23-8-2011).pdf

376-MUMNP-2011-CORRESPONDENCE(25-3-2011).pdf

376-MUMNP-2011-CORRESPONDENCE(5-10-2012).pdf

376-mumnp-2011-correspondence.pdf

376-mumnp-2011-description(complete).pdf

376-mumnp-2011-form 1.pdf

376-mumnp-2011-form 13.pdf

376-MUMNP-2011-FORM 18.pdf

376-mumnp-2011-form 2(title page).pdf

376-mumnp-2011-form 2.pdf

376-MUMNP-2011-FORM 3(18-11-2013).pdf

376-MUMNP-2011-FORM 3(23-8-2011).pdf

376-MUMNP-2011-FORM 3(5-10-2012).pdf

376-mumnp-2011-form 3.pdf

376-mumnp-2011-form 5.pdf

376-mumnp-2011-form pct-ipea-401.pdf

376-mumnp-2011-form pct-isa-210.pdf

376-mumnp-2011-form pct-ro-101.pdf

376-MUMNP-2011-OTHER DOCUMENT(18-11-2013).pdf

376-mumnp-2011-other document.pdf

376-mumnp-2011-other pct document.pdf

376-MUMNP-2011-PETITION UNDER RULE-137(18-11-2013).pdf

376-MUMNP-2011-POWER OF ATTORNEY(25-3-2011).pdf

376-MUMNP-2011-REPLY TO EXAMINATION REPORT(18-11-2013).pdf

376-mumnp-2011-sequence listing.pdf

376-mumnp-2011-wo international publication report a1.pdf

Claims.pdf

COMPLETE SPECIFICATION.pdf

fer reply.pdf

Marked Copy alongwith Annextures.pdf