High affinity antibodies recognizing core 2 o-glycans of variant muc5ac antigen, compositions containing and uses thereof

Abstract

This invention relates to novel affinity variants of NEO-102, e.g., PB223, which variants bind to core 2 O-glycans of the MUC5AC antigen (comprising core 2 O-glycans), which variant is expressed by different cancers, e.g., lung cancer, ovarian cancer, cervical cancer, stomach cancer, liver cancer, uterine cancer, pancreatic cancer, breast cancer, and colon cancer. This invention also relates to the use of such affinity variants of NEO-102, e.g., PB223 for treating and / or detecting cancers that express such core 2 O-glycans, e.g., lung cancer, ovarian cancer, cervical cancer, uterine cancer, stomach cancer, liver cancer, pancreas cancer, breast cancer, and colon cancer, wherein such treatments optionally may include the use of other active agents and / or treatment regimens used in treating cancer.

Description

ATTY. DOCKET NO.1143282.005213 HIGH AFFINITY ANTIBODIES RECOGNIZING CORE 2 O-GLYCANS OF VARIANT MUC5AC ANTIGEN, COMPOSITIONS CONTAINING AND USES THEREOF RELATED APPLICATIONS This application claims benefit of priority to US Provisional Application No.: 63 / 583,996, filed on September 20, 2023, and 63 / 688,904 August 30, 2024 the contents of which are hereby incorporated by reference in their entirety. SEQUENCE DISCLOSURE This application includes as part of its disclosure a biological electronic sequence listing contained in the file entitled 1143282o005213 (Size: 219,331 bytes; and Date of Creation: September 18, 2024), which is hereby incorporated by reference in its entirety. SEQUENCES NOT PERMITTED TO BE ENTERED IN ST.26 XML FILE DUE TO SEQUENCE LENGTH Table A below lists sequences present in this application but were omitted in the XML sequence listing due to the length of the sequences. SequenceLengthType Organism Other Information 2 FIELThe present application generally relates to novel high affinity monoclonal antibodies which recognize variant forms of MUC5AC (comprising core 2 O-glycans) and specific glycans which are expressed specifically by human pancreatic, colorectal and other cancers. The present application also relates to the use thereof as cancer diagnostics and therapeutics. Exemplary embodiments provide methods wherein cancer is detected, diagnosed, monitored, and / or treated using the inventive novel high affinity monoclonal antibodies. These high affinity monoclonal antibodies may be used as a monotherapy or in combination therapies, i.e., which include the administration of an antibody as disclosed herein and another anti-cancer agent or cancer regime, e.g., another anti-tumor antibody, checkpoint inhibitor fusion protein, chemotherapeutic, toxin, checkpoint inhibitor antibody or cytokine, chimeric antigen receptor (CAR)-T and CAR-NK.ATTY. DOCKET NO.1143282.005213 BACKGROUND Cancer is caused by a malfunction in the growth control systems of a cell. Cells control their growth via combination of proliferation inhibition by tumor suppressor genes (e.g., Retinoblastoma protein (pRb), p53) and proliferation activation by oncogenes (proto- oncogenes) (e.g., RAS, WNT, MYC, EKR, and TRK). A mutation in either a tumor suppressor gene and / or a protooncogene in a cell results in unusually high rates of cell proliferation (e.g., a tumor cell). See Knudson (1971) Proc. Natl. Acad. Sci. USA 68(4): 820-823. The cell may exhibit early signs of aberrant growth such as aberrant morphology or unusually large size (hyperplasia). The tumor cells also may proliferate at a higher than usual but not lethal rate, forming a growth, known as benign tumor (dysplasia). In later stages of cancer, the tumor cells proliferate at an unusually high rate resulting in uncontrolled growth that threatens the health of the patient known as malignant tumors (or in situ cancer). Many tumors can "metastasize" or spread throughout the body forming tumors. Metastasis is generally a sign of late stage, terminal cancer. Weinberg (September 1996) "How Cancer Arises" Scientific American 62-70. Prior applications owned by Applicant have described multiple cancer-associated antigens and specific antibodies thereto useful in treating cancers, optionally cancers wherein these antigens are expressed, e.g., WO / 2012 / 040617, WO / 2011 / 163401, WO / 2009 / 062050, WO / 2006 / 113546, U.S. Patent Nos.7,829,678, 7,763,720, and 7,314,622, and U.S. pre-grant publication nos.2012 / 0034227, 2011 / 0165599, 2011 / 0158902, 2011 / 0129416, 2011 / 0076761, 2010 / 0310559, 2009 / 0162931, and 2008 / 0227965, each of which is hereby incorporated by reference in its entirety. These antibodies target different cancer-specific antigens including in particular the “NPC-1 antigen” or the “MUC5AC antigen” (comprising core 2 O-glycans). MUC5AC is a mucin which contains cysteine regions and contributing to the formation of extracellular gels, and it is typically expressed in stomach and respiratory tract. MUC5AC has emerged as a potentially important biomarker as its overexpression has been associated with pancreatic cancer and colon cancer (Byrd JC, Bresalier RS, “Mucins and mucin binding proteins in colorectal cancer”, Cancer Metastasis Rev.2004; 23:77-99). Furthermore, in colon and other cancers, MUC5AC is found in an aberrantly glycosylated form (Patel SP, Bristol A, Saric O, Wang XP et al, “Antitumor activity of a novel monoclonalATTY. DOCKET NO.1143282.005213 antibody NPC-1, optimized for recognition of tumor antigen MUV5AC variant in preclinical models”, Cancer Immunol Immunother 2013, 62:1011-1019). The human mucin (MUC) family consists of members designated MUC1 to MUC21— subclassified into secreted and transmembrane forms. The secreted mucins (e.g., MUC2, MUC5AC, MUC5B and MUC6) form a physical barrier, which acts as a mucous gel that provides protection for epithelial cells that line the respiratory and gastrointestinal tracts and form the ductal surfaces of organs such as the liver, breast, pancreas, and kidney. The transmembrane mucins (e.g., MUC1, MUC4, MUC 13 and MUC 16) have a single membrane-spanning region and contribute to the protective mucous gel through their ectodomains of (9-glycosylated tandem repeats that form rod-like structures. (Kufe (2009) Nature Reviews 9: 874-885). MUC5AC expression is found on apical epithelial cells of the mucus glands of gastric antrum and body, tracheobronchial epithelium, superficial epithelium of the gallbladder and endocervix epithelium. MUC5AC is highly expressed in adenoma. See Kocer, et al. (2006) BMC Gastroenterology 6: 4. Additionally, MUC5AC is expressed in tumors of gastrointestinal, pancreaticobiliary, and endocervical origin (e.g., colon, esophagus, liver, lung, pancreas, stomach, and uterus). See Lau, et al. (2004) Am. J. Clin Pathol.122: 61-69. Also, MUC5AC has been reported to be highly expressed in breast and gastric cancers. (Zhang, et al. (1998) Clinical Cancer Research 4: 2669-2676). Further, MUC5AC glycan variants have been associated with pancreatic neoplasms. (Haab, et al., (May 2010) Annals of Surgery 251(5): 937-945). Also, MUC5AC is aberrantly expressed by colorectal polyps and colorectal carcinoma. Kocer, et al. (2006) BMC Gastroenterology 6(4): 1-9). Approaches such as tumor-targeting monoclonal antibodies (mAb) can be harnessed to stimulate innate anti-cancer immunity. An example thereof is NEO-102 (Ensituximab), which is a chimeric human IgG1 mAb targeting a glycosylated variant of MUC5AC (comprising core 2 O-glycans) with specificity to colorectal, pancreatic and other cancers. The NEO-102 mAb was developed from a colon cancer tumor-associated antigen vaccine preparation (Hollinshead A, Elias EG, Arlen M, et al., “Specific active immunotherapy in patients with adenocarcinoma of the colon utilizing tumor-associated antigen (TAA). A phase I clinical trial”, Cancer 1985; 56:480-489). Its mechanism of action is primarily through antibody-dependent cellular cytotoxicity (ADCC) (Patel SP, Bristol A, Saric O, Wang XP et al.,ATTY. DOCKET NO.1143282.005213 “Antitumor activity of a novel monoclonal antibody NPC-1, optimized for recognition of tumor antigen MUV5AC variant in preclinical models”, Cancer Immunol Immunother 2013, 62:1011-1019). Preclinical data has shown that NEO-102 selectively targets MUC5AC-positive tumors (comprising core 2 O-glycans) and spares MUC5AC antigen-positive nonmalignant tissue (Patel SP, Bristol A, Saric O, Wang XP et al:, “Antitumor activity of a novel monoclonal antibody NPC-1, optimized for recognition of tumor antigen MUC5AC variant in preclinical models”, Cancer Immunol Immunother 2013, 62:1011-1019). Additionally, a single-arm, phase 2 study of NEO-102 was completed, enrolling 63 patients with advanced, refractory colorectal cancer with 53 subjects were treated wherein the median age was 58 years and 46% were female. This study revealed that NEO-102 exhibited favorable tolerability and demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal cancer (Kim RD, Azad NS, Morse MA et al., “Phase II study of Ensituximab, a novel chimeric monoclonal antibody, in adults with unresectable metastatic colorectal cancer”, Clinical Cancer Res 2020;26 (14) 3557-3564). Notwithstanding the foregoing, it would be beneficial to provide novel and improved antibodies which recognize cancer-specific variant forms of MUC5AC, e.g., those which are bound by NEO-102 (comprising core 2 O-glycans), particularly those which possess enhanced antigen binding affinity (lower KD), which detect tumor cells which express low levels of the antigen bound by NEO-102, and / or which elicit greater antitumor potency, alone or in association with other antitumor agents. The present invention achieves these objectives. SUMMARY The invention provides improved high affinity antibodies which target the (comprising core 2 O-glycans) antibodies which target the (comprising core 2 O-glycans) the same (comprising core 2 O-glycans)ATTY. DOCKET NO.1143282.005213 These novel affinity variant antibodies potentially may be used to detect or treat tumors which express low levels of the antigen bound by NEO-102 including tumor cells which are not detected or appreciably bound by NEO-102. Additionally, these novel affinity variant antibodies when used in cancer therapy may elicit greater antitumor potency than NEO-102, alone or in association with other active agents, e.g., other antitumor agents. As noted, the inventive antibodies were obtained by affinity maturation. Affinity maturation and in vitro mutagenesis methods are techniques often used in antibody engineering to modify antibody sequences, because, if successful, they can result in the generation of an antibody variant comprising improved properties in relation to a parental antibody, e.g., improved therapeutic efficacy (Pavoni E, Flego M, Luisa M. et al., “Selection, affinity maturation, and characterization of a human scFv antibody against CEA protein”, BMC Cancer 2006; 6:41; Ko BK, Choi S, Cui LG. et al., “Affinity maturation of monoclonal antibody 1E11 by targeted randomization in CDR3 regions optimizes therapeutic antibody targeting HER2-positive gastric cancer”, PLOS One 2015; 10 (7):e0134600). In vivo, affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response can elicit antibodies with several fold greater affinity than in a primary response. Affinity maturation primarily occurs on membrane immunoglobulin of germinal center B cells and as a direct result of somatic hypermutation (SHM) and selection by TFH cells. This in vivo process is thought to involve two interrelated processes, occurring in the germinal centers of the secondary lymphoid organs: a. Somatic hypermutation: Mutations in the variable, antigen-binding coding sequences (known as complementarity-determining regions (CDRs)) of the immunoglobulin genes. The mutation rate is up to 1,000,000 times higher than in cell lines outside the lymphoid system. Although the exact mechanism of the SHM is still not known, a major role for the activation-induced (cytidine) deaminase has been discussed. The increased mutation rate results in 1-2 mutations per CDR and, hence, per cell generation. The mutations alter the binding specificity and binding affinities of the resultant antibodies. (SeeATTY. DOCKET NO.1143282.005213 Teng, G.; Papavasiliou, F.N. (2007), "Immunoglobulin Somatic Hypermutation". Annu. Rev. Genet.41: 107–120. doi:10.1146 / annurev.genet.41.110306.130340. PMID 17576170; and Roskos L. et al., (2007). Stefan Dübel (ed.). “Handbook of Therapeutic Antibodies”, Weinheim: Wiley-VCH. pp.145–169. ISBN 978-3-527-31453-9. b. Clonal selection: B cells that have undergone SHM must compete for limiting growth resources, including the availability of antigen and paracrine signals from TFH cells. The follicular dendritic cells (FDCs) of the germinal centers present antigen to the B cells, and the B cell progeny with the highest affinities for antigen, having gained a competitive advantage, are favored for positive selection leading to their survival. Positive selection is based on steady cross-talk between TFH cells and their cognate antigen presenting GC B cell. Because a limited number of TFH cells reside in the germinal center, only highly competitive B cells stably conjugate with TFH cells and thus receive T cell-dependent survival signals. B cell progeny that have undergone SHM, but bind antigen with lower affinity will be out-competed, and be deleted. Over several rounds of selection, the resultant secreted antibodies produced will have effectively increased affinities for antigen. Like the natural prototype, in vitro affinity maturation is based on the principles of mutation and selection. In vitro affinity maturation has successfully been used to optimize many antibodies, antibody fragments and other peptide molecules such as antibody mimetics. In vitro affinity maturation techniques find known usage in obtaining antibody variants possessing improved affinity and binding interactions. Relating thereto, many display technologies and maturation methods have been developed over the years, which have been instrumental in the isolation of therapeutic antibodies by the use of affinity maturation. However, due to the inherent limitations in the display capacity of these technologies, and the empirical nature of obtaining antibody variants possessing desired properties, (e.g., those which retain the epitopic binding specificity of the parental antibody, which possess enhanced binding affinity and / or which elicit enhanced therapeutic potency), affinity maturation is still a challenge and success is often unpredictable.ATTY. DOCKET NO.1143282.005213 Based on the foregoing, and the knowledge that NEO-102 demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal cancer (Kim RD, Azad NS, Morse MA et al. “Phase II study of Ensituximab, a novel chimeric monoclonal antibody, in adults with unresectable metastatic colorectal cancer”, Clinical Cancer Res 2020;26 (14) 3557-3564), Applicant conducted saturation mutagenesis of the VH and VL residues of NEO-102 with the hope of obtaining a variant of NEO-102 possessing enhanced binding affinity and potentially enhanced anti-tumor potency. These experiments involved meticulous modification of all of the residues of both the VH and the VL regions of NEO-102. As is disclosed in the examples infra, these experiments culminated in the discovery of several novel high affinity clones (e.g., AHF-18095, AHF-18100 and AHF-18104). Of these novel clones the inventors selected a novel clone which is referred to herein alternatively as “AHF-18095”, “NEO-102m” or “PB223”, for further characterization and clinical development. In the Experimental Example section of this application the methods which were used to obtain and characterize these high affinity clones, the sequences thereof, and in particular the sequences and properties of the PB223 clone and other clones are described. Also, the VH and VL sequences of PB223 are contained in FIG.6 and FIG.7. As is disclosed therein (see results in TABLE 3), the PB223 clone possesses enhanced binding affinity to the target MUC5AC variant antigen (comprising core 2 O- glycans) bound by NEO-102. Whereas the KD of NEO-102 to the target MUC5AC variant antigen (comprising core 2 O-glycans) ranges from 5.60 to 7.38 E-09 (see TABLE 3), the KD of PB223 to the target MUC5AC variant antigen (comprising core 2 O-glycans) is 1.23E-09, i.e., about 4-6-fold better. Moreover, as is shown in TABLE 4, flow cytometry analysis, which compared the binding of NEO-102 and PB223 to different cancer cell lines, demonstrated that PB223 exhibits significantly enhanced binding to some tested tumor cell lines, including two colon cell lines (SW-403, COLO-205), one triple negative breast cell line (TNBC)(HCC1937) and one ovarian cancer cell line (OV-90). These results strongly suggest that the PB223 clone obtained by the use of affinity maturation likely binds to a broader range of tumor types compared to the parental antibody NEO-102, and therefore potentially may be used to detect and / or treat cancers which are not amenable to treatment with NEO-102.ATTY. DOCKET NO.1143282.005213 OBJECTS OF THE INVENTION Accordingly, it is an object of the invention to provide novel variants of NEO-102 including the PB223 clone and other high affinity clones derived from NEO-102 having the sequences disclosed herein. Also, it is a specific object of the invention to provide an antibody or antibody fragment which is an affinity variant of NEO-102, which antibody or antibody fragment binds to the same MUC5AC variant antigen (comprising core 2 O-glycans) bound by NEO-102, and which comprises a KD which is at least 2-fold, 3-fold or 4-fold greater lesser (greater affinity) than that of NEO-102. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises a variable heavy (VH) region and a variable light (VL) region comprising one or more of the following mutations relative to NEO-102: (i) (S→E) modificaƟon of VH residue 28, (ii) (N→I) modificaƟon of VH (CDR1) residue 35; (iii) (G→K) modificaƟon of VH (CDR2) residue 62; (v) (S→V) modificaƟon at VH (CDR2) residue 58; (vi) (A→G) modificaƟon of VL (CDR2) posiƟon 54; and a variable heavy (VH) region comprising (S→L) modificaƟon of VH (CDR2) residue 61 (relaƟve to NEO-102). Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises at least 2, 3, 4 or 5 of the above modifications. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises a variable heavy (VH) region and a variable light (VL) region comprising all the following mutations relative to NEO-102: (i) (S→E) modification of VH residue 28, (ii) (N→I) modificaƟon of VH (CDR1) residue 35; and (iii) (G→K) modificaƟon of VH (CDR2) residue 62 (relaƟve to NEO-102). Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises a variable heavy (VH) region and a variable light (VL) region comprising all the following mutations relative to NEO-102: (i) (S→E) modification of VH residue 28, (ii) (N→I) modificaƟon of VH (CDR1) residue 35; (iii) (G→K) modification of VH (CDR2) residue 62; (iv) (S→V) modificaƟon of VH (CDR2) residue 58; and (v) (A→G) modificaƟon of VL (CDR2) posiƟon 54 (relaƟve to NEO-102).ATTY. DOCKET NO.1143282.005213 Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises a variable heavy (VH) region and a variable light (VL) region comprising all the following mutations relative to NEO-102: (i) (S→E) modification at VH residue 28, (ii) (N→I) modificaƟon of VH (CDR1) residue 35; (iii) (G→K) modification of VH (CDR2) residue 62; and (S→L) modificaƟon of VH (CDR2) residue 61 (relative to NEO-102). Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises the identical CDRs as PB223, AHF-18104 or AHF-18100. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises (i) a VH polypeptide possessing an amino acid sequence which possesses at least 90% sequence identity to the VH polypeptide of NEO-102, and (ii) a VL polypeptide possessing an amino acid sequence which possesses at least 90% sequence identity to the VL polypeptide of NEO-102. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises (i) a VH polypeptide possessing an amino acid sequence which possesses at least 95% sequence identity to the VH polypeptide of NEO-102, and (ii) a VL polypeptide possessing an amino acid sequence which possesses at least 95% sequence identity to the VL polypeptide of NEO-102. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises (i) a VH polypeptide possessing an amino acid sequence which possesses at least 98-99% sequence identity to the VH polypeptide of NEO-102 (excluding the modifications), and (ii) a VL polypeptide possessing an amino acid sequence which possesses at least 98-99% sequence identity to the VL polypeptide of NEO- 102. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises (i) a VH polypeptide possessing an amino acid sequence which is identical to the VH polypeptide of PB223, and (ii) a VL polypeptide which is identical to the VL polypeptide of PB223.ATTY. DOCKET NO.1143282.005213 Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises (i) a VH polypeptide possessing an amino acid sequence which is identical to the VH polypeptide of AHF-18104, and (ii) a VL polypeptide which is identical to the VL polypeptide of AHF-18104. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises (i) a VH polypeptide possessing an amino acid sequence which is identical to the VH polypeptide of AHF-18100, and (ii) a VL polypeptide which is identical to the VL polypeptide of AHF-18100. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises an Fc or constant region, optionally a human Fc or constant region. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises a human IgG1, IgG2, IgG3 or IgG4 Fc or constant region, which optionally comprises at least one modification that enhances or inhibits at least one antibody effector function. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises a Fab or scFv. Also, it is a specific object of the invention to provide an antibody or antibody fragment as above described, which comprises a human IgG1, IgG2, IgG3 or IgG4 Fc or constant region, which comprises at least one modification that enhances or inhibits at least one antibody effector function selected from glycosylation, FcR binding, FcRN binding, phagocytosis, antibody dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC). An immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) comprising an antibody or antibody fragment according to any of the foregoing. Also, it is a specific object of the invention to provide an antibody or antibody fragment according to any of the foregoing, or immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) comprising same, which is expressed in a recombinant host cell, optionally a mammalian, yeast, fungal, plant, insect or bacterial cell.ATTY. DOCKET NO.1143282.005213 Also, it is a specific object of the invention to provide an antibody or antibody fragment according to any of the foregoing, or immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) comprising same, which is expressed in a CHO, BHK, COS, Hela or HEK cell. Also, it is a specific object of the invention to provide a nucleic acid or nucleic acids which encode for an antibody, antibody fragment, immunoconjugate, ADC, or CAR according to any of foregoing. Also, it is a specific object of the invention to provide an expression vector comprising the nucleic acid or nucleic acids of the foregoing. Also, it is a specific object of the invention to provide a recombinant cell which comprises an expression vector according to the foregoing, optionally is mammalian, yeast, fungal, plant, insect or bacterial cell, further optionally a CHO, BHK, COS or Hela or HEK cell. Also, it is a specific object of the invention to provide a diagnostic or therapeutic composition comprising an antibody or antibody fragment, immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) according to any one of the foregoing and a therapeutically or diagnostically acceptable carrier. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method comprising the administration of an antibody or antibody fragment, immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) according to any one of the foregoing and at least one other therapeutic agent, optionally wherein said other therapeutic agent comprises an anti-cancer agent. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to the foregoing, wherein said other therapeutic agent comprises a checkpoint inhibitor antibody or checkpoint inhibitor fusion protein, a hormone, a cytokine, a growth factor, a chemotherapeutic, another anti-cancer antibody, or a combination of any of the foregoing. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to the foregoing, wherein said other therapeutic agent targets the extrinsic apoptotic pathway.ATTY. DOCKET NO.1143282.005213 Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to the foregoing, wherein said other therapeutic agent targets the intrinsic apoptotic pathway. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to the foregoing, wherein said other therapeutic agent targets the common apoptotic pathway. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent enhances ADCC of cancer cells. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises gemcitabine and / or cisplatin. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises a death receptor (DR) agonist, optionally a DR ligand or fragment or variant thereof, further optionally TRAIL or a Fas ligand, TNF receptor 1 (TNFRI), TRAIL-R2, DR4, DR5, or CD95 (APO-1 / Fas). Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic according to any of the foregoing, wherein the other therapeutic agent activates said death receptor or sensitizes said death receptor to activation by another agent. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises an extrinsic pathway agent that agonizes the extrinsic apoptotic pathway in cancer cells, optionally wherein said extrinsic pathway agent targets PML-RARα, DR4 (TRAIL R1), and / or DR5 (TRAIL R2), further optionally wherein said extrinsic pathway agent comprises TRAIL polypeptide or an agonistic fragment thereof, a Dr4 agonist, a Dr5 agonist, or all trans retinoic acid (ATRA). Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeuticATTY. DOCKET NO.1143282.005213 agent comprises an Dr4 or Dr5 agonist, optionally an agonistic anti-Dr4 or anti-Dr5 monoclonal antibody, optionally selected from Apomab, HGS-ETR1, HGS-ETR2, and GS-TR2J. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises necrosis factor alpha (TNF-alpha), tumor necrosis factor beta (TNF-beta, lymphotoxin alpha), lymphotoxin beta (LT-beta), TRAIL (Apo2L), CD95 (Fas, APO-I) ligand, TRAMP (DR3, Apo-3) ligand, DR4 ligand, DR6 ligand as well as fragments, variants, and derivatives thereof. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises an anti-CD95 antibody, anti-TRAIL-R1 (DR4) antibody, anti-TRAIL-R2 (DR5) antibody, anti-DR6 antibody, anti TNF-R1 / 2 antibody and anti-TRAMP (DR3) antibody or a fragment or derivative thereof. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises mapatumumab (HGS-ETR1), lexatumumab (HGS-ETR2), conatumumab (AMG655), dulanermin (AMG 951, APO2L / TRAIL, PRO1762, RG3639, rhApo2L / TRAIL), tigatuzumab (CS1008), TRAIL R (DR4-Specific Altrimer, Anaphore), HGS TR2J, LBY135, drozitumab (PR085780, apomab), SL231, SM164 with TRAIL R2, or TAS266. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises a chemotherapeutic agent, optionally doxorubicin, etoposide, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, oxaliplatin, 2-deoxy-D-glucose, or a platin, or comprises a drug that targets a Fas pathway or a c-FLIP pathway. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises 4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH), estradiol (E2), or delta-tocotrienol. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeuticATTY. DOCKET NO.1143282.005213 agent comprises an intrinsic pathway agent that agonizes the intrinsic apoptotic pathway in cancer cells, optionally wherein said intrinsic pathway agent comprises an agonist of a proapoptotic Bcl-2 family member, further optionally wherein said proapoptotic BCL-2 family member comprises Bax, Bak, Bad, Bcl-Xs, Bid, Bik, Bim, or Hrk or comprises an antagonist of an antiapoptotic Bcl-2 family member, optionally wherein said antiapoptotic Bcl-2 family member comprises Bcl-2, Bcl-XL, Bcl-W, Bfl-1, pr Mcl-1. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises an agent that targets Bcl-1, BcI-XL, Bax, BCL-Xs and / or PML-RARα, optionally an agent that acts directly on the mitochondrial inner membrane, and agent that antagonizes the antiapoptotic members of the Bcl-2 protein family, or an agent that enhances the activity of the proapoptotic members of the Bcl-2 family of proteins such as Bax or comprises arsenic trioxide or lonidamine. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein the other therapeutic agent comprises an antisense agent targeting Bcl-1, Bcl-XL, Bax, BCL-Xs, both Bcl-2 and Bcl- XL, clusterin, or comprises oblimersen sodium. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent is an intrinsic pathway agent which comprises a small molecule, optionally a small molecule that recognizes the surface pocket of Bcl-2 or Bcl-XL or comprises Antimycin-A, HA14-1, synthetic BH3 organic peptides, or a derivative thereof. or comprises farnesyl- thiosalicylic acid (FTS), estradiol (E2),delta-tocotrienol, salinomycin, or curcumin. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises an antimetabolite, alkylator, corticosteroid, radiation, monoclonal antibody, platin or PARP inhibitor. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeuticATTY. DOCKET NO.1143282.005213 agent comprises epirubicin, cisplatin, dacarbazine, fludarabine / cyclophosphamide, dexamethasone, or doxorubicin. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises FTS, CMH, TMS, estradiol (E2). Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises a cytostatic agent, cytocidal agent, actinomycin D, adriamycin, arsenic trioxide, asparaginase, bleomycin, busulfan, camptosar, carboplatinum, carmustine, chlorambucil, cisplatin, corticosteroids, colicheamicin, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fludarabine, fluorouracil, gemcitabine, gemcitabine, gemzar, hydroxyurea, idarubicin, ifosfamide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, mitomycin, mitoxantrone, oxaliplatin, paclitaxel, platinol, platinex, procarbazine, raltitrexed, ricin, steroids, streptozocin, taxol, taxotere, thioguanine, thiotepa, tomudex, topotecan, treosulfan, trihydrate, vinblastine, vincristine, vindesine, vinorelbine, vinorelbine, daunomycin, dactinomycin, esorubicin, mafosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, mitomycin C, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, hexamethylmelamine, pentamethylmelamine, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, deoxyco-formycin, 4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5- fluorodeoxyuridine (5-FUdR), colchicine, trimetrexate, teniposide, or diethylstilbestrol. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises a DNA damaging agent, nucleophosmin, an agent which induces cellular damage as part of an enhanced or synergistic process with another agent, a catalytic antibody, prodrugs, CHK1 / 2 inhibitor, CBP-501, AZD7762, histone deacetylase inhibitor, vorinostat, tumour necrosis factor related apoptosis inducing ligand, BH3 mimetic, ABT737, small molecule inhibitors, tyrosine kinase inhibitors, imatinib mesylate, gefitinib, erlotinib, monoclonal antibodies, rituximab or trastuzumab.ATTY. DOCKET NO.1143282.005213 Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises a caspase activator, apoptin, or survivin. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises an endocrine therapeutic, a biologic response modifier, interferon, interleukin, antibody, aptamer, siRNA, oligonucleotide, enzyme, ion channel and receptor inhibitor or activator, hyperthermia, cryotherapy, agent to attenuate any adverse effects, or antiemetic. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises an alkylating drug, mechlorethamine, chlorambucil, Cyclophosphamide, Melphalan, Ifosfamide, antimetabolite, Methotrexate, purine antagonist, pyrimidine antagonist, 6-Mercaptopurine, 5-Fluorouracil, Cytarabine, Gemcitabine, spindle poison, Vinblastine, Vincristine, Vinorelbine, Paclitaxel, podophyllotoxin, Etoposide, Irinotecan, Topotecan, antibiotic, doxorubicin, Bleomycin, Mitomycin, nitrosoureas, Carmustine, Lomustine, inorganic ion, Cisplatin, Carboplatin, enzyme, Asparaginase, hormone, Tamoxifen, Leuprolide, Flutamide, or Megestrol. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises an agent that targets p53, p53 pathway members, IκB kinase, IKKβ, the proteasome / ubiquitin pathway, the 20S proteasome, the PI3K / Akt pathway, or mTOR. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises ONY-015, INGN201, PS1145, Bortezomib, CCI779, RAD-001, or an siRNA targeting MDM2. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises mixed lineage kinase domain like (MLKL) protein, rapamycin (RAP) or derivatives and / or analogs thereof.ATTY. DOCKET NO.1143282.005213 Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said other therapeutic agent comprises everolimus or RAD001; CCI-779, ABT578, SAR543, vancomycin (an ethyl analog of FK506), AP23573, AP23841, KU-0063794, INK-128, EX2044, EX3855, EX7518, compounds that bind to the ATP-binding cleft of mTOR, AZD08055, or OSIO27. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said affinity variant of NEO-102, optionally PB223 and said second therapeutic agent exhibit enhanced therapeutic efficacy relative to said affinity variant of NEO-102 and said second therapeutic agent administered individually. Also, it is a specific object of the invention to provide a therapeutic composition or therapeutic method according to any of the foregoing, wherein said affinity variant of NEO-102, optionally PB223 and said second therapeutic agent exhibit therapeutic efficacy at a lower dosage than the effective dosage of said affinity variant of NEO-102 or said second therapeutic agent when administered individually. Also, it is a specific object of the invention to provide an antibody or antibody fragment, immunoconjugate, ADC, or CAR composition, or method according to any one of the foregoing, wherein the antibody is chimeric. Also, it is a specific object of the invention to provide an antibody or antibody fragment, immunoconjugate, ADC, or CAR composition, or method according to any one of the foregoing, wherein the antibody or antibody fragment is humanized. Also, it is a specific object of the invention to provide a pharmaceutical composition comprising the antibody or antibody fragment, immunoconjugate, ADC, or CAR, according to any one of the foregoing, and a pharmaceutically acceptable carrier. Also, it is a specific object of the invention to provide a kit comprising the antibody or antibody fragment, immunoconjugate, ADC, or CAR according to any one of the foregoing. Also, it is a specific object of the invention to provide method of treatment, comprising administering an antibody or antibody fragment, immunoconjugate, ADC, orATTY. DOCKET NO.1143282.005213 CAR, or composition containing, or a cell expressing according to any of the foregoing to a subject in need thereof. Also, it is a specific object of the invention to provide a method of treatment, comprising administering an antibody or antibody fragment, immunoconjugate, ADC, or CAR, or composition containing, or a cell expressing according to any of the foregoing to a subject in need thereof and further comprising administering radiation therapy to a subject, optionally wherein said radiation therapy comprises gamma-radiation, neutron beam radiotherapy, electron beam radiotherapy, proton therapy, brachytherapy, and systemic radioactive isotopes, which optionally provides for an enhanced or synergistic improvement in treatment efficacy relative to the additive effects of the antibody and radiation therapy alone. Also, it is a specific object of the invention to provide a treatment method of any one of the foregoing, wherein said affinity variant of NEO-102 and said second therapeutic agent are administered to said subject together or separately and / or in combination. Also, it is a specific object of the invention to provide a treatment method of any one of the foregoing, wherein said treatment results in apoptosis of cancer cells in said subject. Also, it is a specific object of the invention to provide a treatment method of any one of the foregoing, wherein said cancer is selected from the group consisting of: a carcinoma, colon cancer, pancreatic cancer, lung cancer, prostate cancer, liver cancer, adenoma, melanoma, breast cancer, ovarian cancer, uterine cancer, cervical cancer, mesothelioma, and skin cancer. Also, it is a specific object of the invention to provide a method of detecting a variant MUC5AC antigen (comprising core 2 O-glycans) or cancer cells which express said variant MUC5AC antigen (comprising core 2 O-glycans) using an antibody or antibody fragment according to any of the foregoing, which is effected in vivo and / or in vitro, which optionally is used to assess the disease status of a subject or optionally to assess the treatment status of a subject, optionally after administration of an antibody or antibody fragment, immunoconjugate, ADC, or CAR, or composition according to any one of theATTY. DOCKET NO.1143282.005213 foregoing or a cell which expresses antibody or antibody fragment, immunoconjugate, ADC, or CAR according to any one of the foregoing. Also, it is an object of the invention to provide therapeutic compositions comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein and a pharmaceutically acceptable carrier or excipient and optionally another therapeutic, e.g., another anticancer agent. Also, it is an object of the invention to provide diagnostic compositions comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein and a diagnostically acceptable carrier or excipient. Also, it is an object of the invention to provide immunoconjugates or antibody drug conjugates and compositions containing which immunoconjugates or antibody drug conjugates comprise a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein which are directly or indirectly attached to a desired moiety, e.g., a chemotherapeutic, small molecule, label, radionuclide, toxin, nucleic acid or nucleic acid complex (e.g., mRNA, siRNA, ribonucleoprotein complex used in gene editing, etc.), cytokine, hormone, growth factor, et seq. Also, it is an object of the invention to provide chimeric antigen receptors (CARs) comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein which are directly or indirectly attached to a desired moiety, e.g., a signaling moiety, a chemotherapeutic, small molecule, label, radionuclide, nucleic acid or nucleic acid complex (e.g., mRNA, siRNA, ribonucleoprotein complex used in gene editing, etc.), cytokine, hormone, growth factor, et seq. Also, it is an object of the invention to provide nucleic acids which encode for a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein, or a CAR, immunoconjugate or ADCATTY. DOCKET NO.1143282.005213 comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein. Also, it is an object of the invention to provide expression vectors comprising nucleic acids which encode for a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein, or expression vectors which comprise a nucleic acid which encodes a CAR, immunoconjugate or ADC comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein. Also, it is an object of the invention to provide recombinant cells, e.g., mammalian, bacterial, yeast, insect, and more specifically CHO cells which express nucleic acids which encode for a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein, or which express a nucleic acid which encodes a CAR, immunoconjugate or ADC comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein. In the case of CAR expressing cells, the recombinant cells will typically be immune cells, e.g., human immune cells, e.g., T lymphocytes (e.g., CD4+ T cells, CD8+ T cells, Tregs, Tsupp, etc.); NK cells, among others. Also, it is an object of the invention to provide methods of using such recombinant cells, e.g., mammalian, bacterial, yeast, insect, and more specifically CHO, BHK, COS, HeLa, or HEK cells to express a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein, or to express a CAR, immunoconjugate or ADC comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein. Also, it is an object of the invention to provide therapeutic methods comprising the use of the clone PB223 and other high affinity clones disclosed infra for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers,ATTY. DOCKET NO.1143282.005213 Also, it is an object of the invention to provide therapeutic methods comprising the use of the clone PB223 and other high affinity clones disclosed infra for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, Also, it is an object of the invention to provide therapeutic methods and compositions for use in such methods comprising the use of the clone PB223 and other high affinity clones disclosed infra in combination with another therapeutic agent, wherein the high affinity clone PB223 and the other agent may be in the same or different compositions; or used in combination with another cancer treatment regimen for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, optionally wherein the combination provides for enhanced therapeutic efficacy, e.g., a synergistic enhancement of antitumor efficacy. Also, it is an object of the invention to provide methods for selecting patients for treatment in a therapeutic regimen involving the use of the inventive variants of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102. Said patient may be a patient with a cancer ( prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, ). The patient may be selected for treatment based upon the presence of a cancer at a specified stage, such as pre-cancer and Stage I, II, II and IV cancers including metastatic cancers, optionally wherein said cancer may express the antigen bound by PB223, may comprise a cancer or pre-cancer of the prostate, skin (e.g., melanoma), ovary, cervix, uterus, , or a metastatic cancer cells originating from any of said tissues or organs.ATTY. DOCKET NO.1143282.005213 Also, it is an object of the invention to provide therapeutic methods and compositions for use in such methods comprising the use of the clone PB223 and other high affinity clones disclosed infra in combination with another therapeutic agent, wherein the high affinity clone PB223 and the other agent may be in the same or different compositions; for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the other agent is selected from other therapeutic antibodies, checkpoint inhibitors, chemotherapeutics, and the like, which optionally result in enhanced therapeutic efficacy relative to the individual therapeutic agents, optionally by triggering apoptotic pathways, enhancing ADCC, enhancing CDC, and thereby promote tumor regression, enhanced cell killing, or increased patient survival. Also, it is an object of the invention to provide the use of NEO-102 affinity variants, including the clone PB223 or other high affinity clones derived from NEO-102 for detecting MUC5AC (comprising core 2 O-glycans) expressing cells in vivo or in patient samples and based thereon monitoring the disease status of cancers characterized by variant MUC5AC expression (comprising core 2 O-glycans), e.g., prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, . Also, it is an object of the invention to provide therapeutic methods comprising the use of one of the disclosed variants of NEO-102 including the clone PB223 and other cancer treatment methods, such as surgery, radiotherapy (e.g., gamma-radiation, neutron beam radiotherapy, electron beam radiotherapy, proton therapy, brachytherapy, and systemic radioactive isotopes, to name a few), endocrine therapy, biologic response modifiers (interferons, interleukins, antibodies, aptamers, siRNAs, oligonucleotides, enzymes, ion channel and receptor inhibitors or activators to name a-few), hyperthermia and cryotherapy, agents to attenuate any adverse effects (e.g., antiemetics), and other approved chemotherapeutic drugs, including, but not limited to, alkylating drugs (e.g., mechlorethamine, chlorambucil, Cyclophosphamide, Melphalan, Ifosfamide),ATTY. DOCKET NO.1143282.005213 antimetabolites (e.g., Methotrexate), purine antagonists and pyrimidine antagonists (e.g., 6- Mercaptopurine, 5-Fluorouracil, Cytarabine, Gemcitabine), spindle poisons (e.g., Vinblastine, Vincristine, Vinorelbine, Paclitaxel), podophyllotoxins (e.g., Etoposide, Irinotecan, Topotecan), antibiotics (Doxorubicin, Bleomycin, Mitomycin), nitrosoureas (e.g., Carmustine, Lomustine), inorganic ions (e.g., Cisplatin, Carboplatin), enzymes (e.g., Asparaginase), and hormones (e.g., Tamoxifen, Leuprolide, Flutamide, and Megestrol),among others. Also, it is a specific object of the invention to provide pharmaceutical compositions which comprise a therapeutically effective amount of with one of the inventive variants of NEO-102 including the clone PB223 formulated together with one or more pharmaceutically acceptable carriers and optionally one or more other active agents such as one or more of those above-identified. As used herein, the term "pharmaceutically acceptable carrier" means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type which optionally can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), buccally, or as an oral or nasal spray. Also, it is a specific object of the invention to provide methods including any of the therapeutic or diagnostic methods afore mentioned, wherein an affinity variant of NEO- 102, e.g. clone PB223 or another of the variants disclosed herein is administered in combination with any of the anti-cancer antibodies disclosed in the table below. TABLE 1: Antibodies which selectively bind NPC-1, 16C3, or 31-1 epitopes.ATTY. DOCKET NO.1143282.005213Leucine in CH1 and Methionine at residue 390 to Threonine in CH3. Also, it is a specific object of the invention to provide methods of using the disclosed affinity variants of NEO-102, including PB223 and fragments thereof to detect cancer specific antigens in vitro and in vivo. Also, it is a specific object of the invention to provide methods of using the disclosed affinity variants of NEO-102, including PB223 and fragments thereof to stage cancer prognosis, design specific treatment regimens, and / or to establish the efficacy of a specific treatments. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1. This figure depicts an array of 94 O-glycan structures which were screened to identify which if any O-glycans that PB223 binds. FIG.2A & 2B. These figures contain the structures of the 94 O-glycan structures of the O-glycans in the array shown in FIG.1, which were used to test the O-glycan binding activity of clone PB223.ATTY. DOCKET NO.1143282.005213 FIG.3. This figure contains microarray data analyzed using Mapix software (Innopsys) obtained in binding experiments using PB223 screened against the O-glycan microarray of FIG.1 which comprises the O-glycan structures in . The microarray data revealed that PB223 binds to O-glycans which are terminated with α (2,6) sialic acids, which glycan group includes both sTn antigens (03 and 04) as well as other O- glycans (030, 053, and 083). FIG.4. This figure contains microarray data analyzed using Mapix software (Innopsys). In the experiments corresponding to the microarray data shown in the FIG. the antibody PB223 concentration was 10 µg / mL or 2 µg / mL. The results revealed that the anti- human IgG Fc region (Cy3) does not interact with any of the O-glycans in the O-glycan array of FIG.1. FIG.5. This figure contains a schematic of different O-glycans including Core-2 O- glycans which are bound by PB223. FIG.6 contains the VH and VL sequences of AHF-18095 or PB223. In the FIG. the CDR residues are in red and the mutated residues are underlined. FIG.7 contains an alignment of the VH and VL sequences of NEO-102 and PB223. In the FIG. the CDR residues are in red font and the mutated residues in the CDRs and in the frameworks are underlined and in green font. FIG.8 contains flow cytometry analysis evaluating the binding of Herceptin to SK- BR-3 cells (human breast cancer cell line). FIG.9 contains flow cytometry analysis evaluating the binding of PB223 to OV-90 cells (human ovarian cancer cell line). FIG. 10 and FIG. 11 contain exemplary results of internalization analysis of Herceptin and PB223 with their respective cell lines over various concentrations and time intervals. FIG. 12 contains the dose-dependent responses of Herceptin with SK-BR-3 at 48 hours (system control). FIG. 13 contains the dose-dependent responses of PB223, when incubated with OV-90 cells at 48 hours.ATTY. DOCKET NO.1143282.005213 FIG.14, 15, and 16 contain flow cytometry analysis evaluating the binding of PB223 to OV-90, HCC-1937 and LOVO cell lines, respectively. FIG.17 contains flow cytometry analysis evaluating the binding of PB223) to K562 cells (human chronic leukemia cell line). FIG.18 through FIG.37 represent positive IHC images (DAB chromogen staining as seen by brown color), while FIG.38 and FIG.39 illustrate two negative IHC images (absence of DAB chromogen staining as seen by absence of brown color). FIG. 18 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to stomach cancer cells. FIG. 19 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to esophageal cancer cells. FIG. 20 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to colon cancer cells. FIG. 21 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to colon cancer cells. FIG. 22 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to Hepatocellular carcinoma cells. FIG. 23 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to pancreatic cancer cells. FIG. 24 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to lung papillary adenocarcinoma cells. FIG. 25 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to thyroid cancer cells. FIG.26 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to head and neck cancer cells. FIG. 27 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to breast cancer cells.ATTY. DOCKET NO.1143282.005213 FIG. 28 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to ovarian cancer cells. FIG. 29 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to Endometrioid adenocarcinoma cells. FIG.30 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to cervical cancer cells. FIG. 31 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to prostate cancer cells. FIG. 32 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to testicular cancer cells. FIG.33 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to kidney cancer cells. FIG. 34 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to bladder cancer cells. FIG. 35 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to OV-90 cancer cells. FIG. 36 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to Triple negative breast cancer cells. FIG. 37 contains an IHC image obtained using DAB chromogen staining showing that PB223 binds to Triple negative breast cancer cells. FIG.38 contains an IHC image obtained using DAB chromogen staining showing that PB223 does not bind to skin cancer cells (negative staining). FIG.39 contains an IHC image obtained using DAB chromogen staining showing that PB223 does not bind to thyroid cancer cells (negative staining). FIG.40 through 49 contain negative IHC images (as shown by the absence of DAB chromogen staining, i.e., no brown color visible). The tissues stained in these figures is described below.ATTY. DOCKET NO.1143282.005213 FIG.40 contains an IHC image obtained using DAB chromogen staining showing that PB223 does not bind to normal brain tissue stained with PB223. FIG.41: contains an IHC image obtained using DAB chromogen staining showing that the isotype control does not bind to normal brain tissue. FIG.42 contains an IHC image obtained using DAB chromogen staining showing that PB223 does not bind to normal liver tissue. FIG.43 contains an IHC image obtained using DAB chromogen staining showing that the isotype control does not bind to normal liver tissue. FIG.44 contains an IHC image obtained using DAB chromogen staining showing that PB223 does not bind to normal lung tissue. FIG.45 contains an IHC image obtained using DAB chromogen staining showing that the isotype control does not bind to normal lung tissue. FIG.46 contains an IHC image obtained using DAB chromogen staining showing that PB223 does not bind to normal colon tissue. FIG.47 contains an IHC image obtained using DAB chromogen staining showing that the isotype control does not bind to normal colon tissue. FIG.48 contains an IHC image obtained using DAB chromogen staining showing that PB223 does not bind to normal lymph node tissues. FIG.49 contains an IHC image obtained using DAB chromogen staining showing that the isotype control does not bind to normal lymph node tissues. FIG. 50 contains an IHC image showing the staining of a human colon cancer sample with the isotype control antibody. FIG. 51 contains an IHC image showing the staining of a human colon cancer sample with NEO-102. FIG. 52 contains an IHC image showing the staining of a human cervical cancer sample with the isotype control antibody. FIG. 53 contains an IHC image showing the staining of a human cervical cancer sample with NEO-102.ATTY. DOCKET NO.1143282.005213 FIG. 54 contains an IHC image showing the staining of a human prostate cancer sample with the isotype control antibody. FIG. 55 contains an IHC image showing the staining of a human prostate cancer sample with NEO-102. FIG.56 contains an IHC image showing the staining of a human head & neck cancer sample with the isotype control antibody. FIG.57 contains an IHC image showing the staining of a human head & neck cancer sample with NEO-102. FIG. 58 contains an IHC image showing the staining of a human triple negative breast cancer sample with the isotype control antibody. FIG. 59 contains an IHC image showing the staining of a human triple negative breast cancer sample with NEO-102. FIG. 60 contains an IHC image showing the staining of a human bladder cancer sample with the isotype control antibody. FIG. 61 contains an IHC image showing the staining of a human bladder cancer sample with NEO-102. FIG. 62 contains an IHC image showing the staining of a human kidney cancer sample with the isotype control antibody. FIG. 63 contains an IHC image showing the staining of a human kidney cancer sample with NEO-102. FIG.64 contains an IHC image showing the staining of a human liver cancer sample with the isotype control antibody. FIG.65 contains an IHC image showing the staining of a human liver cancer sample with NEO-102. Prior to providing the detailed description of the invention, the following definitions are provided. DEFINITIONSATTY. DOCKET NO.1143282.005213 Unless defined otherwise, all technical and scientific terms used herein have the same meaning as those commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein may be used in the invention or testing of the present invention, suitable methods and materials are described herein. The materials, methods and examples are illustrative only, and are not intended to be limiting. As used in the description herein and throughout the claims that follow, the meaning of "a," "an," and "the" includes plural reference unless the context clearly dictates otherwise. "Adjuvant," as used herein, refers broadly to any substance which is incorporated into or administered simultaneously with NPC-1 epitope peptidomimetic of the invention which potentiates the immune response in the subject. Adjuvants include but are not limited to aluminum compounds, e.g., gels, aluminum hydroxide and aluminum phosphate, and Freund's complete or incomplete adjuvant (e.g., in which the PS / A antigen is incorporated in the aqueous phase of a stabilized water in paraffin oil emulsion). The paraffin oil may be replaced with different types of oils, e.g., squalene or peanut oil. Other materials with adjuvant properties, include BCG (attenuated Mycobacterium tuberculosis), calcium phosphate, levamisole, Isoprinosine, polyanions (e.g., poly A:U), lentinan, pertussis toxin, lipid A, saponins, QS-21 and peptides, e.g. muramyl dipeptide. Rare earth salts, e.g., lanthanum and cerium, may also be used as adjuvants. The amount of adjuvants depends on the subject and the particular antigen used and can be readily determined by one skilled in the art without undue experimentation. "Amino acid," as used herein, refers broadly to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, butATTY. DOCKET NO.1143282.005213 retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. "Antibody," as used herein, refers broadly to any polypeptide chain-containing molecular structure with a specific shape that fits to and recognizes an epitope, where one or more non-covalent binding interactions stabilize the complex between the molecular structure and the epitope. The archetypal antibody molecule is the immunoglobulin, and all types of immunoglobulins, IgG, IgM, IgA, IgE, IgD, from all sources, e.g., human, rodent, rabbit, cow, sheep, pig, dog, chicken, are considered to be "antibodies." Antibodies include but are not limited to chimeric antibodies, human antibodies and other non-human mammalian antibodies, humanized antibodies, single chain antibodies (scFvs), camelbodies, nanobodies, IgNAR (single-chain antibodies derived from sharks), small-modular immunopharmaceuticals (SMIPs), and antibody fragments (e.g., Fabs, Fab', F(ab')2.) Numerous antibody coding sequences have been described; and others may be raised by methods well-known in the art. See Streltsov, et al. (2005) Protein Sci.14(11): 2901-9; Greenberg, et al. (1995) Nature 374(6518): 168-173; Nuttall, et al. (2001) Mol Immunol. 38(4): 313-26; Hamers-Casterman, et al. (193) Nature 363(6428): 446-8; Gill, et al. (2006) Curr Opin Biotechnol.17(6): 653-8. The term "antibody" is used in the broadest sense and specifically covers, for example, single monoclonal antibodies (including agonist, antagonist, and neutralizing antibodies), antibody compositions with poly-epitopic specificity, polyclonal antibodies, single chain antibodies, and fragments of antibodies as long as they exhibit the desired biological or immunological activity. The term "immunoglobulin" (Ig) is used interchangeable with antibody herein. An "isolated antibody" is one which has been identified and separated and / or recovered from a component of its natural environment. Contaminant components of its natural environment are materials which would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In preferred embodiments, the antibody will be purified (1) to greater than 95% by weight of antibody as determined by the Lowry method, and mostATTY. DOCKET NO.1143282.005213 preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step. The basic 4-chain antibody unit is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains (an IgM antibody consists of 5 of the basic heterotetramer unit along with an additional polypeptide called J chain, and therefore contain 10 antigen binding sites, while secreted IgA antibodies can polymerize to form polyvalent assemblages comprising 2-5 of the basic 4-chain units along with J chain). In the case of IgGs, the 4-chain unit is generally about 150,000 Daltons. Each L chain is linked to a H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype. Each H and L chain also has regularly spaced intrachain disulfide bridges. Each H chain has at the N-terminus, a variable domain (VH) followed by three constant domains (CH) for each of the alpha and gamma chains and four CH domains for mu and epsilon isotypes. Each L chain has at the N- terminus, a variable domain (VL) followed by a constant domain (CL) at its other end. The VL is aligned with the VH and the CL is aligned with the first constant domain of the heavy chain (CH1). Particular amino acid residues are believed to form an interface between the light chain and heavy chain variable domains. The pairing of a VH and VL together forms a single antigen-binding site. For the structure and properties of the different classes of antibodies, see, e.g., Basic and Clinical Immunology, 8th edition, Daniel P. Stites, Abba I. Terr and Tristram G. Parslow (eds.), Appleton & Lange, Norwalk, Conn., 1994, page 71 and Chapter 6. The L chain from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains (CH), immunoglobulins can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, having heavy chains designated alpha, delta, epsilon, gamma, and mu, respectively. The gamma and alphaATTY. DOCKET NO.1143282.005213 classes are further divided into subclasses on the basis of relatively minor differences in CH sequence and function, e.g., humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The term "variable" refers to the fact that certain segments of the variable domains differ extensively in sequence among antibodies. The V domain mediates antigen binding and define specificity of a particular antibody for its particular antigen. However, the variability is not evenly distributed across the 110-amino acid span of the variable domains. Instead, the V regions consist of relatively invariant stretches called framework regions (FRs) of 15-30 amino acids separated by shorter regions of extreme variability called "hypervariable regions" that are each 9-12 amino acids long. The variable domains of native heavy and light chains each comprise four FRs, largely adopting a beta-sheet configuration, connected by three hypervariable regions, which form loops connecting, and in some cases forming part of, the beta-sheet structure. The hypervariable regions in each chain are held together in close proximity by the FRs and, with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al., “Sequences of Proteins of Immunological Interest”, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)). The constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in antibody dependent cellular cytotoxicity (ADCC). The term "monoclonal antibody" 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 are highly specific, being directed against a single antigenic site. Furthermore, in contrast to polyclonal antibody preparations which include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they may be synthesized uncontaminated by other antibodies. The modifier "monoclonal" is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies useful in the present invention may be prepared by the hybridoma methodology first described by Kohler et al., Nature, 256:495 (1975), or may beATTY. DOCKET NO.1143282.005213 made using recombinant DNA methods in bacterial, eukaryotic animal or plant cells (see, e.g., U.S. Pat. No.4,816,567). The "monoclonal antibodies" may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature, 352:624-628 (1991) and Marks et al., J. Mol Biol., 222:581-597 (1991), for example. The monoclonal antibodies herein 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, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see U.S. Pat. No.4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)). Chimeric antibodies of interest herein include "primatized" antibodies comprising variable domain antigen-binding sequences derived from a non-human primate (e.g. Old World Monkey, Ape etc), and human constant region sequences. An "intact" antibody is one which comprises an antigen-binding site as well as a CL and at least heavy chain constant domains, CH1, CH2 and CH3. The constant domains may be native sequence constant domains (e.g. human native sequence constant domains) or amino acid sequence variant thereof. Preferably, the intact antibody has one or more effector functions. "Antibody fragments" comprise a portion of an intact antibody, preferably the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies (see U.S. Pat. No. 5,641,870, Example 2; Zapata et al., Protein Eng.8(10): 1057-1062

[1995] ); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produces two identical antigen-binding fragments, called "Fab" fragments, and a residual "Fc" fragment, a designation reflecting the ability to crystallize readily. The Fab fragment consists of an entire L chain along with the variable region domain of the H chain (VH), and the first constant domain of one heavy chain (CH1). Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab')2 fragmentATTY. DOCKET NO.1143282.005213 which roughly corresponds to two disulfide linked Fab fragments having divalent antigen- binding activity and is still capable of cross-linking antigen. Fab' fragments differ from Fab fragments by having additional few residues at the carboxy terminus of the CH1 domain including one or more cysteines from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab')2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known. The Fc fragment comprises the carboxy-terminal portions of both H chains held together by disulfides. The effector functions of antibodies are determined by sequences in the Fc region, which region is also the part recognized by Fc receptors (FcR) found on certain types of cells. "Fv" is the minimum antibody fragment which contains a complete antigen- recognition and -binding site. This fragment consists of a dimer of one heavy- and one light- chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops each from the H and L chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site. "Single-chain Fv" also abbreviated as "sFv" or "scFv" are antibody fragments that comprise the VH and VL antibody domains connected into a single polypeptide chain. Preferably, the sFv polypeptide further comprises a polypeptide linker between the VH and VL domains which enables the sFv to form the desired structure for antigen binding. For a review of sFv, see Pluckthun in “The Pharmacology of Monoclonal Antibodies”, Vol.113, Rosenburg and Moore eds., Springer-Verlag, New York, pp.269-315 (1994). The term "diabodies" refers to small antibody fragments prepared by constructing sFv fragments (see preceding paragraph) with short linkers (about 5-10 residues) between the VH and VL domains such that inter-chain but not intra-chain pairing of the V domains is achieved, resulting in a bivalent fragment, i.e., fragment having two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" sFvATTY. DOCKET NO.1143282.005213 fragments in which the VH and VL domains of the two antibodies are present on different polypeptide chains. Diabodies are described more fully in, for example, EP 404,097; WO 93 / 11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993). "Humanized" forms of non-human (e.g., rodent) antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody. For the most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or non-human primate having the desired antibody specificity, affinity, and capability. In some instances, framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non- human immunoglobulin and all or substantially all of the FRs are those of a human immunoglobulin sequence. The humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature 321:522-525 (1986); Reichmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol.2:593-596 (1992). A "species-dependent antibody," e.g., a mammalian anti-human IgE antibody, is an antibody which has a stronger binding affinity for an antigen from a first mammalian species than it has for a homologue of that antigen from a second mammalian species. Normally, the species-dependent antibody "bind specifically" to a human antigen (i.e., has a binding affinity (Kd) value of no more than about 10-7M, preferably no more than about 10-8M and most preferably no more than about 10-9M) but has a binding affinity for a homologue of the antigen from a second non-human mammalian species which is at least about 50 fold, or at least about 500 fold, or at least about 1000 fold, weaker than its binding affinity for the human antigen. The species-dependent antibody can be of any of the various types of antibodies as defined above, but preferably is a humanized or human antibody.ATTY. DOCKET NO.1143282.005213 The term "variable domain residue numbering as in Kabat" or "amino acid position numbering as in Kabat", and variations thereof, refers to the numbering system used for heavy chain variable domains or light chain variable domains of the compilation of antibodies in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991). Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or CDR of the variable domain. For example, a heavy chain variable domain may include a single amino acid insert (residue 52a according to Kabat) after residue 52 of H2 and inserted residues (e.g. residues 82a, 82b, and 82c, etc according to Kabat) after heavy chain FR residue 82. The Kabat numbering of residues may be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a "standard" Kabat numbered sequence. Additionally, when referring to a modified Fc domain or “Fc variant”, the terms “Kabat numbering system,” “Kabat position,” “Kabat residue,” “Kabat number” or the like, or in any instance in which an Fc modification is identified by number without reference to a specific numbering system (e.g., “position” followed by a number), refer to positions numbered according to the EU index or EU numbering scheme (Kabat et al., 1991, “Sequences of Proteins of Immunological Interest”, 5th Ed., United States Public Health Service, National Institutes of Health, Bethesda, incorporated by reference). The terms “EU index” or “EU index as in Kabat” and the like refer to the numbering of the EU antibody (Edelman et al., 1969, Proc Natl Acad Sci USA 63:78-85, incorporated by reference). Additionally, except where stated otherwise, when referring to an Fc variant relative terms (such as “increased” or “decreased”) refer to the change in that attribute relative to the same Fc variant (or polypeptide containing said Fc variant) without said modification. Antibody "effector functions" refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary with the antibody isotype. Examples of antibody effector functions include: C1q binding and complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation. Exemplary antibodies of the present disclosure may include one or more modifications that decrease one or moreATTY. DOCKET NO.1143282.005213 effector functions, such as alterations in the amino acid sequence, or alterations in the location, extent, or type of glycosylation. "Complement dependent cytotoxicity" or "CDC" refers to the lysis of a target cell in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to antibodies (of the appropriate subclass) which are bound to their cognate antigen. To assess complement activation, a CDC assay, e.g., as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996), may be performed. Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a form of cytotoxicity in which secreted Ig bound onto Fc receptors (FcRs) present on certain cytotoxic cells (e.g., Natural Killer (NK) cells, neutrophils, and macrophages) enable these cytotoxic effector cells to bind specifically to an antigen-bearing target cell and subsequently kill the target cell with cytotoxins. The antibodies "arm" the cytotoxic cells and are absolutely required for such killing. The primary cells for mediating ADCC, NK cells, express Fc gamma RIII only, whereas monocytes express Fc gamma RI, Fc gamma RII and Fc gamma RIII. FcR expression on hematopoietic cells is summarized in TABLE 3 on page 464 of Ravetch and Kinet, Annu Rev. Immunol.9:457-92 (1991). To assess ADCC activity of a molecule of interest, an in vitro ADCC assay, such as that described in U.S. Pat. No.5,500,362 or 5,821,337 may be performed. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes et al. Proc. Natl. Acad. Sci., USA 95:652-656 (1998). "Antigen," as used herein, refers broadly to a molecule or a portion of a molecule capable of being bound by an antibody which is additionally capable of inducing an animal to produce an antibody capable of binding to an epitope of that antigen. An antigen may have one epitope, or have more than one epitope. The specific reaction referred to herein indicates that the antigen will react, in a highly selective manner, with its corresponding antibody and not with the multitude of other antibodies which may be evoked by other antigens. Antigens may be tumor specific (e.g., expressed by neoplastic cells of pancreatic and colon carcinoma.)ATTY. DOCKET NO.1143282.005213 "Antigenic composition," as used herein, refers broadly to a composition that elicits an immune response. "Cancer," as used herein, refers broadly to any neoplastic disease (whether invasive or metastatic) characterized by abnormal and uncontrolled cell division causing malignant growth or tumor. "Chimeric antibody," as used herein, refers broadly to an antibody molecule in which the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and / or species, or an entirely different molecule which confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug; or the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity. "Conservatively modified variants," as used herein, applies to both amino acid and nucleic acid sequences, and with respect to particular nucleic acid sequences, refers broadly to conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given protein. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) may be modified to yield a functionally identical molecule. "Complementarity determining region," "hypervariable region," or "CDR," as used herein, refers broadly to one or more of the hyper-variable or complementarily determining regions (CDRs) found in the variable regions of light or heavy chains of an antibody. See Kabat, et al. (1987) "Sequences of Proteins of Immunological Interest" National Institutes of Health, Bethesda, MD. These expressions include the hypervariable regions as defined by Kabat, et al (1991) "Sequences of Proteins of Immunological Interest" U.S. Dept. of Health and Human Services, or the hypervariable loops in 3-dimensionaIATTY. DOCKET NO.1143282.005213 structures of antibodies. Chothia and Lesk (1987) J Mol. Biol.196: 901- 17. The CDRs in each chain are held in close proximity by framework regions and, with the CDRs from the other chain, contribute to the formation of the antigen binding site. Within the CDRs there are select amino acids that have been described as the selectivity determining regions (SDRs) which represent the critical contact residues used by the CDR in the antibody-antigen interaction. Kashmiri (2005) Methods 36: 25-34. "Control amount," as used herein, refers broadly to a marker can be any amount or a range of amounts to be compared against a test amount of a marker. For example, a control amount of a marker may be the amount of a marker in a patient with a particular disease or condition or a person without such a disease or condition. A control amount can be either in absolute amount (e.g., microgram / ml) or a relative amount (e.g., relative intensity of signals). "Differentially present," as used herein, refers broadly to differences in the quantity or quality of a marker present in a sample taken from patients having a disease or condition as compared to a comparable sample taken from patients who do not have one of the diseases or conditions. For example, a nucleic acid fragment may optionally be differentially present between the two samples if the amount of the nucleic acid fragment in one sample is significantly different from the amount of the nucleic acid fragment in the other sample, for example as measured by hybridization and / or NAT-based assays. A polypeptide is differentially present between the two samples if the amount of the polypeptide in one sample is significantly different from the amount of the polypeptide in the other sample. It should be noted that if the marker is detectable in one sample and not detectable in the other, then such a marker may be considered to be differentially present. Optionally, a relatively low amount of up-regulation may serve as the marker. "Diagnostic," as used herein, refers broadly to identifying the presence or nature of a pathologic condition. Diagnostic methods differ in their sensitivity and specificity. The "sensitivity" of a diagnostic assay is the percentage of diseased individuals who test positive (percent of "true positives"). Diseased individuals not detected by the assay are "false negatives." Subjects who are not diseased and who test negative in the assay are termed "true negatives." The "specificity" of a diagnostic assay is 1 minus the false positive rate, where the "false positive" rate is defined as the proportion of those without the diseaseATTY. DOCKET NO.1143282.005213 who test positive. While a particular diagnostic method may not provide a definitive diagnosis of a condition, it suffices if the method provides a positive indication that aids in diagnosis. "Diagnosing," as used herein, refers broadly to classifying a disease or a symptom, determining a severity of the disease, monitoring disease progression, forecasting an outcome of a disease and / or prospects of recovery. The term "detecting" may also optionally encompass any of the foregoing. Diagnosis of a disease according to the present invention may, in some embodiments, be affected by determining a level of a polynucleotide or a polypeptide of the present invention in a biological sample obtained from the subject, wherein the level determined can be correlated with predisposition to, or presence or absence of the disease. It should be noted that a "biological sample obtained from the subject" may also optionally comprise a sample that has not been physically removed from the subject. An "effective amount" of a composition such as a polypeptide, drug, siRNA or analog thereof, antibody, pharmaceutical, small molecule, or other compound, or an agonist or antagonist thereof, is an amount sufficient to carry out a specifically stated purpose. An "effective amount" may be determined empirically and in a routine manner, in relation to the stated purpose. "Expression vector," as used herein, refers broadly to any recombinant expression system for the purpose of expressing a nucleic acid sequence of the invention in vitro or in vivo, constitutively or inducibly, in any cell, including prokaryotic, yeast, fungal, plant, insect or mammalian cell. The term includes linear or circular expression systems. The term includes expression systems that remain episomal or integrate into the host cell genome. The expression systems can have the ability to self-replicate or not, i.e., drive only transient expression in a cell. The term includes recombinant expression cassettes which contain only the minimum elements needed for transcription of the recombinant nucleic acid. "Framework region" or "FR," as used herein, refers broadly to one or more of the framework regions within the variable regions of the light and heavy chains of an antibody. See Kabat, et al (1987) "Sequences of Proteins of Immunological Interest," National Institutes of Health, Bethesda, MD. These expressions include those amino acid sequenceATTY. DOCKET NO.1143282.005213 regions interposed between the CDRs within the variable regions of the light and heavy chains of an antibody. "Heterologous," as used herein, refers broadly to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein). "High affinity," as used herein, refers broadly to an antibody having a dissociation constant of about or less than 10-8M, more preferably about or less than 10-9M and even more preferably about or less than 10-10M for a target antigen. However, "high affinity" binding can vary for other antibody isotypes. For example, "high affinity" binding for an IgM isotype refers to an antibody having a dissociation constant of about or less than 10-7M and even more preferably about or less than 10-8M for a target antigen. "Homology," as used herein, refers broadly to a degree of similarity between a nucleic acid sequence and a reference nucleic acid sequence or between a polypeptide sequence and a reference polypeptide sequence. Homology may be partial or complete. Complete homology indicates that the nucleic acid or amino acid sequences are identical. A partially homologous nucleic acid or amino acid sequence is one that is not identical to the reference nucleic acid or amino acid sequence. The degree of homology can be determined by sequence comparison. The term "sequence identity" may be used interchangeably with "homology." "Host cell," as used herein, refers broadly to a cell that contains an expression vector and supports the replication or expression of the expression vector. Host cells may be prokaryotic cells such as E. coli, or eukaryotic cells such as yeast, insect (e.g., SF9), amphibian, or mammalian cells such as CHO, HeLa, HEK-293, e.g., cultured cells, explants, and cells in vitro.ATTY. DOCKET NO.1143282.005213 "Hybridization," as used herein, refers broadly to the physical interaction of complementary (including partially complementary) polynucleotide strands by the formation of hydrogen bonds between complementary nucleotides when the strands are arranged antiparallel to each other. Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) and consecutive administration in any order. "Carriers" as used herein include pharmaceutically acceptable carriers, excipients, or stabilizers which are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution. Examples of physiologically acceptable carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt- forming counterions such as sodium; and / or nonionic surfactants such as TWEEN®, polyethylene glycol (PEG), and PLURONICS®. "K-assoc" or "Ka", as used herein, refers broadly to the association rate of a particular antibody-antigen interaction, whereas the term "Kdiss" or "Kd," as used herein, refers to the dissociation rate of a particular antibody-antigen interaction. The term "KD", as used herein, is intended to refer to the dissociation constant, which is obtained from the ratio of Kd to Ka (i.e. , Kd / Ka) and is expressed as a molar concentration (M). KD values for antibodies can be determined using methods well established in the art. "Immunoassay," as used herein, refers broadly to an assay that uses an antibody to specifically bind an antigen. The immunoassay may be characterized by the use of specific binding properties of a particular antibody to isolate, target, and / or quantify the antigen. "Isolated," as used herein, refers broadly to material removed from its original environment in which it naturally occurs, and thus is altered by the hand of man from its natural environment. Isolated material may be, for example, exogenous nucleic acidATTY. DOCKET NO.1143282.005213 included in a vector system, exogenous nucleic acid contained within a host cell, or any material which has been removed from its original environment and thus altered by the hand of man (e.g., "isolated antibody”). "Label" or a "detectable moiety" as used herein, refers broadly to a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. "Low stringency," "medium stringency," "high stringency," or "very high stringency conditions," as used herein, refers broadly to conditions for nucleic acid hybridization and washing. Guidance for performing hybridization reactions can be found in Ausubel, et al. (2002) “Short Protocols in Molecular Biology”, (5th Ed.) John Wiley & Sons, NY. Exemplary specific hybridization conditions include but are not limited to: (1) low stringency hybridization conditions in 6X sodium chloride / sodium citrate (SSC) at about 45°C, followed by two washes in 0.2XSSC, 0.1 % SDS at least at 50°C (the temperature of the washes can be increased to 55°C for low stringency conditions); (2) medium stringency hybridization conditions in 6XSSC at about 45°C, followed by one or more washes in 0.2XSSC, 0.1 % SDS at 60°C; (3) high stringency hybridization conditions in 6XSSC at about 45°C, followed by one or more washes in 0.2XSSC, 0.1 % SDS at 65°C; and (4) very high stringency hybridization conditions are 0.5M sodium phosphate, 7% SDS at 65°C, followed by one or more washes at 0.2XSSC, 1 % SDS at 65°C. "Mammal," as used herein, refers broadly to any and all warm-blooded vertebrate animals of the class Mammalia, including humans, characterized by a covering of hair on the skin and, in the female, milk-producing mammary glands for nourishing the young. Examples of mammals include but are not limited to alpacas, armadillos, capybaras, cats, camels, chimpanzees, chinchillas, cattle, dogs, gerbils, goats, gorillas, hamsters, horses, humans, lemurs, llamas, mice, non-human primates, pigs, rats, sheep, shrews, squirrels, and tapirs. Mammals include but are not limited to bovine, canine, equine, feline, murine, ovine, porcine, primate, and rodent species. Mammal also includes any and all those listed on the Mammal Species of the World maintained by the National Museum of Natural History, Smithsonian Institution in Washington DC. "Nucleic acid" or "nucleic acid sequence," as used herein, refers broadly to a deoxy-ribonucleotide or ribonucleotide oligonucleotide in either single- or double-strandedATTY. DOCKET NO.1143282.005213 form. The term encompasses nucleic acids, i.e., oligonucleotides, containing known analogs of natural nucleotides. The term also encompasses nucleic-acid-like structures with synthetic backbones. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences, as well as the sequence explicitly indicated. The term nucleic acid is used interchangeably with gene, cDNA, mRNA, oligonucleotide, and polynucleotide. A nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, "operably linked" means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. "Paratope," as used herein, refers broadly to the part of an antibody which recognizes an antigen (e.g., the antigen-binding site of an antibody.) Paratopes may be a small region (e.g., 15-22 amino acids) of the antibody's Fv region and may contain parts of the antibody's heavy and light chains. See Goldsby, et al. Antigens (Chapter 3) Immunology (5th Ed.) New York: W.H. Freeman and Company, pages 57-75. "Patient," as used herein, refers broadly to any animal who is in need of treatment either to alleviate a disease state or to prevent the occurrence or reoccurrence of a disease state. Also, "Patient" as used herein, refers broadly to any animal who has risk factors, a history of disease, susceptibility, symptoms, signs, was previously diagnosed, is at risk for, or is a member of a patient population for a disease. The patient may be a clinical patient such as a human or a veterinary patient such as a companion, domesticated, livestock, exotic, or zoo animal. The term "subject" may be used interchangeably with the term "patient".ATTY. DOCKET NO.1143282.005213 "Peptidomimetic," as used herein refers broadly to a compound that can imitate or block the biological effect of a peptide on a molecular level. Peptidomimetics may be polymers designed to mimic a peptide, such as peptoids and β-peptides, or may be a peptide that mimics a different peptide. "Polypeptide," "peptide" and "protein," are used interchangeably and refer broadly to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer. Polypeptides can be modified, e.g., by the addition of carbohydrate residues to form glycoproteins. The terms "polypeptide," "peptide" and "protein" include glycoproteins, as well as non-glycoproteins. "Promoter," as used herein, refers broadly to an array of nucleic acid sequences that direct transcription of a nucleic acid. As used herein, a promoter includes necessary nucleic acid sequences near the start site of transcription, such as, in the case of a polymerase II type promoter, a TATA element. A promoter also optionally includes distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. A "constitutive" promoter is a promoter that is active under most environmental and developmental conditions. An "inducible" promoter is a promoter that is active under environmental or developmental regulation. "Prophylactically effective amount," as used herein, refers broadly to the amount of a compound that, when administered to a patient for prophylaxis of a disease or prevention of the reoccurrence of a disease, is sufficient to effect such prophylaxis for the disease or reoccurrence. The prophylactically effective amount may be an amount effective to prevent the incidence of signs and / or symptoms. The "prophylactically effective amount" may vary depending on the disease and its severity and the age, weight, medical history, predisposition to conditions, preexisting conditions, of the patient to be treated. "Prophylaxis," as used herein, refers broadly to a course of therapy where signs and / or symptoms are not present in the patient, are in remission, or were previously present in a patient. Prophylaxis includes preventing disease occurring subsequent toATTY. DOCKET NO.1143282.005213 treatment of a disease in a patient. Further, prevention includes treating patients who may potentially develop the disease, especially patients who are susceptible to the disease (e.g.., members of a patent population, those with risk factors, or at risk for developing the disease). "Recombinant" as used herein, refers broadly with reference to a product, e.g.., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, for example, recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all. "Specifically (or selectively) binds" to an antibody or "specifically (or selectively) immunoreactive with," or "specifically interacts or binds," as used herein, refers broadly to a protein or peptide (or other epitope), refers, in some embodiments, to a binding reaction that is determinative of the presence of the protein in a heterogeneous population of proteins and other biologics. For example, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times greater than the background (non-specific signal) and do not substantially bind in a significant amount to other proteins present in the sample. Typically a specific or selective reaction will be at least twice background signal or noise and more typically more than about 10 to 100 times background. "Specifically hybridizable" and "complementary" as used herein, refer broadly to a nucleic acid can form hydrogen bond(s) with another nucleic acid sequence by either traditional Watson-Crick or other non-traditional types. The binding free energy for a nucleic acid molecule with its complementary sequence is sufficient to allow the relevant function of the nucleic acid to proceed, e.g., RNAi activity. Determination of binding free energies for nucleic acid molecules is well known in the art. See, e.g., Turner, et al. (187) CSH Syrnp. Quant. Biol. LII: 123-33; Frier, et al (1986) PNAS 83: 9373-77; Turner, et al. (1987) J. Am. Chem. Soc.109: 3783-85. A percent complementarity indicates the percentage of contiguous residues in a nucleic acid molecule that can form hydrogen bonds (e.g., Watson- Crick base pairing) with a second nucleic acid sequence (e.g., about at least 5, 6, 7, 8, 9,10ATTY. DOCKET NO.1143282.005213 out of 10 being about at least 50%, 60%, 70%, 80%, 90%, and 100% complementary, inclusive). "Perfectly complementary" or 100% complementarity refers broadly all of the contiguous residues of a nucleic acid sequence hydrogen bonding with the same number of contiguous residues in a second nucleic acid sequence. "Substantial complementarity" refers to polynucleotide strands exhibiting about at least 90% complementarity, excluding regions of the polynucleotide strands, such as overhangs, that are selected so as to be noncomplementary. Specific binding requires a sufficient degree of complementarity to avoid non-specific binding of the oligomeric compound to non-target sequences under conditions in which specific binding is desired, i.e., under physiological conditions in the case of in vivo assays or therapeutic treatment, or in the case of in vitro assays, under conditions in which the assays are performed. The non-target sequences typically may differ by at least 5 nucleotides. "Signs" of disease, as used herein, refers broadly to any abnormality indicative of disease, discoverable on examination of the patient; an objective indication of disease, in contrast to a symptom, which is a subjective indication of disease. "Solid support," "support," "substrate," or "solid phase" as used herein, refer to a non-aqueous matrix to which an antibody or other molecule of the present invention can adhere or attach. Examples of solid phases encompassed herein include those formed partially or entirely of glass (e.g., controlled pore glass), polysaccharides (e.g., agarose), 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 it is a purification column (e.g., an affinity chromatography column). This term also includes a discontinuous solid phase of discrete particles, such as those described in U.S. Pat. No. 4,275,149. The definition broadly includes any material that provides a solid or semi-solid structure with which another material can be attached including but not limited to smooth supports (e.g., metal, glass, plastic, silicon, and ceramic surfaces) as well as textured and porous materials. "Subjects" as used herein, refers broadly to anyone suitable to be treated according to the present invention include, but are not limited to, avian and mammalian subjects, and are preferably mammalian. Mammals of the present invention include, but are not limited to, canines, felines, bovines, caprines, equines, ovines, porcines, rodents (e.g.,ATTY. DOCKET NO.1143282.005213 rats and mice), lagomorphs, primates, and humans. Any mammalian subject in need of being treated according to the present invention is suitable. Human subjects of both genders and at any stage of development (i.e., neonate, infant, juvenile, adolescent, adult) can be treated according to the present invention. The present invention may also be carried out on animal subjects, particularly mammalian subjects such as mice, rats, dogs, cats, cattle, goats, sheep, and horses for veterinary purposes, and for drug screening and drug development purposes. "Subjects" is used interchangeably with "patients." "Symptoms" of disease as used herein, refers broadly to any morbid phenomenon or departure from the normal in structure, function, or sensation, experienced by the patient and indicative of disease. "Treating" or "treatment" or "alleviation" refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented. A subject or mammal is successfully "treated" for a cancer if, after receiving a therapeutic amount of an antibody (or other drug), the patient shows observable and / or measurable reduction in or absence of one or more of the following: reduction in the number of cancer cells or absence of the cancer cells; reduction in the tumor size; inhibition (i.e., slow to some extent and preferably stop) of cancer cell infiltration into peripheral organs including the spread of cancer into soft tissue and bone; inhibition (i.e., slow to some extent and preferably stop) of tumor metastasis; inhibition, to some extent, of tumor growth; and / or relief to some extent, one or more of the symptoms associated with the specific cancer; reduced morbidity and mortality, and improvement in quality of life issues. To the extent the antibody may prevent growth and / or kill existing cancer cells, it may be cytostatic and / or cytotoxic. Reduction of these signs or symptoms may also be felt by the patient. The term "therapeutically effective amount" refers to an amount of an antibody, polypeptide, or other drug effective to "treat" a disease or disorder in a subject or mammal. In the case of cancer, the therapeutically effective amount of the drug may reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to someATTY. DOCKET NO.1143282.005213 extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and / or relieve to some extent one or more of the symptoms associated with the cancer. See the definition herein of "treating". To the extent the drug may prevent growth and / or kill existing cancer cells, it may be cytostatic and / or cytotoxic. The term “synergistic effect” refers to the result achieved using a combination being greater than the sum of the results that would be achieved using the individual components of the combination. For example, in the context of a treatment method (e.g., treatment of cancer), a synergistic effect indicates that the effect of two or more treatments in combination (e.g., two or more of administration of an antibody, a chemotherapeutic agent, another anti-cancer agent, surgery, or radiation) have an effect that is more than just the additive effect of the individual agents. In an exemplary embodiment, the synergistic effect can be measured with respect to tumor burden, mean survival, or another endpoint as known in the art. For example, without intent to be limited by theory, one treatment (such as radiation or chemotherapy, e.g., gemcitabine) may induced increased expression of a cancer-associated antigen, such as the NPC-1, 16C3, or 31.1 antigen, thereby making the cancer cell more susceptible to antibody binding and / or effector function. "Variable region" or "VR," as used herein, refers broadly to the domains within each pair of light and heavy chains in an antibody that are involved directly in binding the antibody to the antigen. 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 (VL) at one end and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain. "Vector," as used herein, refers broadly to a plasmid, cosmid, phagemid, phage DNA, or other DNA molecule which is able to replicate autonomously in a host cell, and which is characterized by one or a small number of restriction endonuclease recognition sites at which such DNA sequences may be cut in a determinable fashion without loss of an essential biological function of the vector, and into which DNA may be inserted in order to bring about its replication and cloning. The vector may further contain a marker suitable for use in the identification of cells transformed with the vector.ATTY. DOCKET NO.1143282.005213 DETAILED DESCRIPTION OF THE INVENTION figures Applicant conducted mutagenesis experiments with the goal of obtaining a variant of NEO-102 possessing enhanced binding affinity and potentially enhanced anti-tumor potency. These experiments involved meticulous modification of all of the residues of both the VH and the VL of NEO-102 and resulted in the creation of several novel high affinity clones (see TABLE 3). Of the novel clones having the VH and VL sequences in TABLE 3 the inventors selected one clone which is referred to herein as AHF-18095 or PB223, which clone has been subjected to further characterization, and based on these results this clone is to be used for clinical development, in particular for use in the treatment of different cancers that express O-glycan antigens bound by NEO-102 and PB223 clone. The VH and VL sequences of AHF-18095 or PB223 are contained in FIG 6. Additionally, FIG.7 contains an alignment of AHF-18095 or PB223 and NEO-102 and shows the modified residues of AHF- 18095 or PB223 relative to NEO-102. Applicant discloses in detail in the Experimental Example section of this application the methods which were used to obtain and characterize these high affinity clones, and in particular the PB223 clone. Based on this characterization the PB223 clone possesses the greatest enhancement in binding affinity to the target MUC5AC antigen (comprising core 2 O-glycans) (relative to NEO-102). Whereas the KD of NEO-102 for to the target MUC5AC antigen (comprising core 2 O-glycans) ranges from 5.60 to 7.38 E-09, the KD of PB223 for the target MUC5AC antigen (comprising core 2 O-glycans) is 1.23E-09, i.e., about 3-6 fold better. Moreover, as is shown in TABLE 4, flow cytometry analysis which compared the binding of NEO-102 and PB223 to different cancer cell lines demonstrated that the clone PB223 exhibits significantly enhanced binding to several tumor cell lines, including two colon (SW-403, COLO-205), one triple negative breast (TNBC)(HCC1937) and one ovarian cancer cell line (OV-90). These results strongly suggest that the PB223 clone obtained by use of saturation mutagenesis binds to a broader range of tumor types compared to the parental antibody NEO-102, and based thereon potentially may be used to treat and / or detect cancers not amenable to treatment or detection with NEO-102 , and / or result in antitumorATTY. DOCKET NO.1143282.005213 potency at lower antibody doses (e.g., when used as a monotherapy or in conjunction with other actives or cancer treatments). The present disclosure therefore also provides therapeutic compositions comprising an affinity variant of NEO-102, optionally PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, or another of the variants having the sequences disclosed in TABLE 3, and further optionally comprising another therapeutic agent. Preferred agents, when co-administered with the affinity variant of NEO-102, may result in enhanced therapeutic efficacy in the patient, e.g., increased cancer cell killing, tumor regression, and / or increased patient survival. The present disclosure also provides therapeutic methods comprising administering said affinity variant of NEO-102, e.g., PB223 and fragments thereof comprising the VH and VL sequences shown in FIG.6 and FIG.7, or another of the variants having the sequences disclosed in TABLE 3, and another therapeutic agent or therapeutic regimen to a patient in need thereof. Said therapeutic regimen may include the combined or separate administration of another anti-cancer agent. Exemplary embodiments of the invention provide a therapeutic method comprising administering an effective amount of said affinity variant of NEO-102, e.g., PB223 and fragments thereof comprising the VH and VL sequences shown in FIG.6 and FIG. 7, or another of the variants having the sequences disclosed in TABLE 3, to a patient, optionally in combination with another therapy or therapeutic agent e.g., one that targets an apoptotic pathway (such as the common, extrinsic or intrinsic apoptotic pathway). Said affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, may optionally contain an Fc or constant region, further optionally one comprising one or more modifications which increase effector functions. For example, said antibody may contain one or more modifications that increase ADCC, which may result in increased ADCC relative to the same antibody sequence lacking said modification. As a further example, said antibody may contain one or modifications that result in increased binding to one or more Fc receptors, thereby resulting in increased Fc receptor binding relative to the same antibody sequence lacking said modification. As a yet further example, said antibody may contain one or more modifications that result inATTY. DOCKET NO.1143282.005213 increased CDC, thereby resulting in increased CDC relative to the same antibody sequence lacking said modification. The present disclosure specifically describes novel variants of NEO-102 including the clone PB223) comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, as well as antibodies comprising the same CDRs as any of novel variants of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed herein. The present disclosure also specifically describes therapeutic compositions comprising a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, and a pharmaceutically acceptable carrier or excipient and optionally another therapeutic, e.g., another anticancer agent. The present disclosure also specifically describes diagnostic compositions comprising a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, and a diagnostically acceptable carrier or excipient. The present disclosure also specifically describes diagnostic methods that comprise the use of a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, to detect cancer cells that express the antigen bound by NEO-102 in vivo and / or in vitro. The present disclosure also specifically describes imaging methods that comprise the use of a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, to image tumors expressing the antigen bound by NEO-102 which images may be used to determine appropriate treatment methods. The present disclosure also specifically describes methods of determining the disease status of a subject that comprise the use of a novel variant of NEO-102 including theATTY. DOCKET NO.1143282.005213 clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, to detect the level of antigen and / or number of cancer cells that express the antigen bound by NEO- 102 in vivo and / or in vitro. These methods may be used in detecting disease status before, during and after treatment with a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed herein and / or another anti- cancer agent. IMMUNOCONJUGATES AND CARS COMPRISING A NEO-102 AFFINITY VARIANT ACCORDING TO THE INVENTION The present disclosure also specifically describes immunoconjugates or antibody drug conjugates and compositions containing which immunoconjugates or antibody drug conjugates which comprise a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, which is directly or indirectly attached to a desired moiety, e.g., a chemotherapeutic, small molecule, label, radionuclide, nucleic acid or nucleic acid complex (e.g., mRNA, siRNA, ribonucleoprotein complex used in gene editing, etc.), cytokine, hormone, growth factor, et seq. The present disclosure also specifically describes chimeric antigen receptors (CARs) comprising a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, which clone is directly or indirectly attached to a desired moiety, e.g., a signaling moiety, a chemotherapeutic, small molecule, label, radionuclide, nucleic acid or nucleic acid complex (e.g., mRNA, siRNA, ribonucleoprotein complex used in gene editing, etc.), cytokine, hormone, growth factor, et seq. The present disclosure also specifically describes nucleic acids which encode for a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed herein, or a CAR, immunoconjugate or ADC comprising a novel variantATTY. DOCKET NO.1143282.005213 of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3. The present disclosure also specifically describes expression vectors comprising nucleic acids which encode for a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3, or expression vectors which comprise a nucleic acid which encodes a CAR, immunoconjugate or ADC comprising a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed herein. The present disclosure also specifically describes recombinant cells, e.g., mammalian, bacterial, yeast, insect, and more specifically CHO, HEK or HeLa cells which comprise expression vectors comprising nucleic acids which encode for a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed herein, or expression vectors which comprise a nucleic acid which encodes a CAR, immunoconjugate or ADC comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3. The present disclosure also specifically describes methods of using such recombinant cells, e.g., mammalian, bacterial, yeast, insect, and more specifically CHO cells to express a novel variant of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones derived from NEO-102 having the sequences disclosed herein, or to express a CAR, immunoconjugate or ADC comprising a novel variant of NEO-102 including the clone PB223 and other high affinity clones derived from NEO-102 having the sequences disclosed in TABLE 3. The present disclosure also specifically describes therapeutic methods comprising the use of the PB223 clone comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra (TABLE 3) for treating cancers characterized by the expression of the (comprising core 2 O-glycans)ATTY. DOCKET NO.1143282.005213 prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, The present disclosure also specifically describes therapeutic methods comprising the use of the PB223 clone and other high affinity clones disclosed in TABLE 3 infra for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, COMBINATION THERAPIES The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the PB223 clone comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed in TABLE 3 infra in combination with another therapeutic agent, wherein the high affinity clone PB223 and the other agent may be in the same or different compositions; or in combination with another cancer treatment regimen for treating cancers, e.g., cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, optionally wherein the combination provides for enhanced therapeutic efficacy, e.g., a synergistic enhancement of antitumor efficacy. The present disclosure also specifically describes methods for selecting patients for treatment in a therapeutic regimen involving the use of the inventive variants of NEO- 102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG. 7, and other high affinity clones derived from NEO-102. Said patient may be a patient with a cancer ( prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, ). The patient may be selected for treatment based upon the presence of a cancer at a specified stage, such as pre-cancer and Stage I, II, II and IV cancers including metastatic cancers. Said cancer may express the antigen boundATTY. DOCKET NO.1143282.005213 by PB223, e.g., cancer or pre-cancer of the colon, pancreas, lung (e.g., mesothelioma), prostate, skin (e.g., melanoma), breast, liver, adenoma, ovary, cervix, or uterus, or a metastatic cancer cells originating from said tissue or organ. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra (TABLE 3) in combination with another therapeutic agent, wherein the high affinity clone PB223 and the other agent may be in the same or different compositions; for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the other agent is selected from other therapeutic antibodies, checkpoint inhibitors, chemotherapeutics, and the like, which optionally result in enhanced therapeutic efficacy relative to the individual therapeutic agents, optionally by triggering apoptotic pathways, enhancing ADCC, enhancing CDC, and thereby promote tumor regression, enhanced cell killing, or increased patient survival. The present disclosure also specifically describes the use of NEO-102 affinity variants, including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, or other high affinity clones derived from NEO-102 for detecting variant MUC5AC (comprising core 2 O-glycans) expressing cells in vivo or in patient samples and based thereon monitoring the disease status of cancers characterized by variant MUC5AC (comprising core 2 O-glycans) expression. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers,ATTY. DOCKET NO.1143282.005213 wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent targets (i.e., activates) the intrinsic apoptosis pathway. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent targets (i.e., activates) the extrinsic apoptosis pathway, optionally wherein such agents include agents that bind to death receptors, such as death receptor ligands (as well as fragments or analogs thereof). anti-death receptor antibodies, e.g., agonistic antibodies that bind to and activate said death receptor, agents that target PML-RARα, DR4 (TRAIL R1), and / or DR5 (TRAIL R2), optionally human TRAIL polypeptide or an agonistic fragment thereof, Dr4 agonists, Dr5 agonists, all trans retinoic acid (ATRA), agonistic anti-Dr4 and anti-Dr5 monoclonal antibodies, respectively, such as Apomab, HGS-ETR1, HGS-ETR2, and HGS-TR2J; or an agent that activates the extrinsic apoptotic pathway, optionally ligands of death receptors are tumor necrosis factor a (TNF- alpha), tumor necrosis factor (TNF-beta, lymphotoxin alpha), lymphotoxin beta (LT-beta), TRAIL (Apo2L), CD95 (Fas, APO-I) ligand, TRAMP (DR3, Apo-3) ligand, DR4 ligand, DR6 ligand as well as fragments, variants, and derivatives of said ligands; TRAIL (Apo2L), an anti-CD95 antibody, anti-TRAIL-R1 (DR4) antibody, anti-TRAIL-R2 (DR5) antibody, anti-DR6 antibody, anti TNF-R1 / 2 antibody and anti-TRAMP (DR3) antibody as well as fragments or derivatives thereof; an anti-TRAIL-R1 (D4) antibody, optionally mapatumumab (HGS-ETR1), an anti- TRAIL-R2 (D5) antibody optionally lexatumumab (HGS-ETR2), conatumumab (AMG655), dulanermin (AMG 951, APO2L / TRAIL, PRO1762, RG3639, rhApo2L / TRAIL), tigatuzumab (CS1008), TRAIL R (DR4-Specific Altrimer, Anaphore), HGS TR2J, LBY135, drozitumab (PR085780, apomab), SL231, SM164 with TRAIL R2, TAS266, and the like; or aATTY. DOCKET NO.1143282.005213 chemotherapeutic agent, optionally one that activate the extrinsic apoptotic pathway, optionally a DNA-damaging agents such as doxorubicin, etoposide, cisplatin or bleomycin or mitomycin C, oxaliplatin, 2-deoxy-D-glucose, drugs that target a Fas pathway, a c-FLIP pathway, 4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH), estradiol (E2), or delta-tocotrienol; an agent that targets Bcl-1, BcI-XL, Bax, BCL-Xs and / or PML-RARα, optionally agents that act directly on the mitochondrial inner membrane, further optionally agents that antagonize the antiapoptotic members of the Bcl-2 protein family, and agents that enhance the activity of the proapoptotic members of the Bcl-2 family of proteins such as Bax such as arsenic trioxide, lonidamine (a derivative of indazole-3-carboxylic acid), antisense agents targeting Bcl-1 (such as Genasense, G3139 or oblimersen sodium), antisense agents targeting Bcl-XL, Bax, and BCL-Xs; antisense agents target both Bcl-2 and Bcl-XL, or target clusterin (also known as testosterone-repressed prostate message 2), small molecules which recognizes the surface pocket of Bcl-2 or Bcl-XL, optionally Antimycin-A and derivatives thereof, HA14-1, synthetic BH3 organic peptides; farnesyl-thiosalicylic acid (FTS), estradiol (E2),delta-tocotrienol, salinomycin, and curcumin. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is selected from antimetabolites, alkylators, corticosteroids, radiation, monoclonal antibodies, platins and PARP inhibitors. Exemplary combinations include use of one of the inventive variants of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, together with epirubicin, cisplatin, dacarbazine, fludarabine / cyclophosphamide, dexamethasone, doxorubicin, or other anti-cancer agents such as FTS, CMH, TMS, and estradiol (E2).ATTY. DOCKET NO.1143282.005213 The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is selected from chemotherapy agents, e.g., alkylating agents, antimetabolites, plant alkaloids, and anti- cancer antibiotics, further optionally one or more selected from cyclophosphamide, cisplatin, carboplatin, oxaliplatin, etoposide, irinotecan, lurbinectedin, paclitaxel, docetaxel, cabazitaxel, altretamine, capecitabine, gemcitabine, ifosfamide, melphalan, pemetrexed, topotecan, vinorelbine, mitoxantrone, ixabepilone, eribulin, estramustine, vinblastine, vincristine, 5-fluorouracil (5-FU), doxorubicin, epirubicin, dactinomycin, or a derivative thereof. In certain embodiments, chemotherapy agents may be selected from cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is selected from biological modifiers such as BCL-2 inhibitor (such as GDC-0199 / ABT-199), lenalidomide (REVLIMID®), a PI3K-delta inhibitor (such as idelalisib (ZYDELIG®)), a PD-1 axis binding antagonist, an agonist, e.g., agonist antibody, directed against an activating co-stimulatory molecule, e.g., CD40, CD226, CD28, OX40 (e.g., AgonOX), GITR, CD137 (also known as TNFRSF9, 4-1 BB, or ILA), CD27 (e.g., CDX-1127), HVEM, or CD127, an antagonist, e.g., antagonist antibody,ATTY. DOCKET NO.1143282.005213 directed against an inhibitory co-stimulatory molecule, e.g., CTLA-4 (also known as CD152), PD-1, TIM-3, BTLA, VISTA, LAG-3, B7-H3, B7-H4, IDO (e.g., 1-methyl-D-tryptophan (also known as 1-D-MT)), TIGIT, MICA / B, GITR (e.g., TRX518) or arginase, ipilimumab (also known as MDX-010, MDX-101, or YERVOY®), tremelimumab (also known as ticilimumab or CP- 675,206, urelumab (also known as BMS-663513), MGA271, an antagonist directed against a TGF beta, e.g., metelimumab (also known as CAT-192), fresolimumab (also known as GC1008), LY2157299k, and an adoptive transfer of a T cell (e.g., a cytotoxic T cell or CTL) expressing a chimeric antigen receptor (CAR), e.g., adoptive transfer of a T cell comprising a dominant-negative TGF beta receptor, e.g., a dominant-negative TGF beta type II receptor. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is an immune checkpoint inhibitor and / or a growth factor or growth factor receptor inhibitor, optionally an inhibitor of PD-L1, PD-1, CTLA-4, VISTA, EGF, EGFR, VEGF, and / or VEGFR, or an antibody or antigen-binding fragment against PD-L1, PD-1, CTLA-4, VISTA, EGF, EGFR, VEGF, and / or VEGFR, or an antibody or antigen-binding fragment against a cancer antigen. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers,ATTY. DOCKET NO.1143282.005213 wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is a chemotherapeutic agent, cytotoxic agent, an anti-hormonal agent, growth inhibitory agent, cytotoxic agent, agent used in radiation therapy, anti-angiogenesis agent, apoptotic agent, anti-tubulin agent, or other agent, such as a epidermal growth factor receptor (EGFR) antagonist (e.g., a tyrosine kinase inhibitor), HER1 / EGFR inhibitor (e.g., erlotinib (TARCEVA™)), platelet derived growth factor inhibitor (e.g., GLEEVEC™ (Imatinib Mesylate)), a COX-2 inhibitor (e.g., celecoxib), interferon, cytokine, antibody other than the anti-CD3 antibody of the disclosure, such as an antibody that bind to one or more of the following targets ErbB2, ErbB3, ErbB4, PDGFR-beta, BIyS, APRIL, BCMA VEGF, or VEGF receptor(s), TRAIL / Apo2, PD-1, PD-L1, PD-L2, or another bioactive or organic chemical agent. In certain embodiments, the additional therapeutic agent(s) may be or may comprise a glucocorticoid, optionally dexamethasone. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is a cytostatic agents, cytocidal agents, actinomycin D, Adriamycin, arsenic trioxide, asparaginase, bleomycin, busulfan, camptosar, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, calicheamicin, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fludarabine, fluorouracil, gemcitabine, gemcitabine, gemzar, hydroxyurea, idarubicin, ifosfamide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, mitomycin, mitoxantrone, oxaliplatin, paclitaxel, platinol, platinex, procarbazine, raltitrexed, ricin, steroids, streptozocin, taxol, Taxotere, thioguanine, thiotepa, tomudex, topotecan, treosulfan, trihydrate, vinblastine, vincristine, vindesine, vinorelbine, vinorelbine, daunomycin, dactinomycin, esorubicin, mafosfamide, cytosine arabinoside, bis- chloroethylnitrosurea, mitomycin C, mithramycin, prednisone, hydroxyprogesterone,ATTY. DOCKET NO.1143282.005213 testosterone, tamoxifen, dacarbazine, hexamethylmelamine, pentamethylmelamine, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, deoxyco- formycin, 4-hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5-FUdR), colchicine, trimetrexate, teniposide, and diethylstilbestrol. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is selected from DNA damaging agents, nucleophosmin, agents which induce cellular damage as part of a synergistic process with another agent, a catalytic antibody, prodrugs, CHK1 / 2 inhibitor, CBP-501, AZD7762, histone deacetylase inhibitor, vorinostat, tumour necrosis factor related apoptosis inducing ligand, BH3 mimetic, ABT737, small molecule inhibitors, tyrosine kinase inhibitors, imatinib mesylate, gefitinib, erlotinib, monoclonal antibodies, rituximab and trastuzumab. The present disclosure also specifically describes therapeutic methods comprising the use of one of the inventive variants of NEO-102 including the clone PB223 and other cancer treatment methods, such as surgery, radiotherapy (in but a few examples, gamma-radiation, neutron beam radiotherapy, electron beam radiotherapy, proton therapy, brachytherapy, and systemic radioactive isotopes, to name a few), endocrine therapy, biologic response modifiers (interferons, interleukins, antibodies, aptamers, siRNAs, oligonucleotides, enzymes, ion channel and receptor inhibitors or activators to name a-few), hyperthermia and cryotherapy, agents to attenuate any adverse effects (e.g., antiemetics), and other approved chemotherapeutic drugs, including, but not limited to, alkylating drugs (e.g., mechlorethamine, chlorambucil, Cyclophosphamide, Melphalan, Ifosfamide), antimetabolites (e.g., Methotrexate), purine antagonists and pyrimidine antagonists (e.g., 6-ATTY. DOCKET NO.1143282.005213 Mercaptopurine, 5-Fluorouracil, Cytarabine, Gemcitabine), spindle poisons (e.g., Vinblastine, Vincristine, Vinorelbine, Paclitaxel), podophyllotoxins (e.g., Etoposide, Irinotecan, Topotecan), antibiotics (Doxorubicin, Bleomycin, Mitomycin), nitrosoureas (e.g., Carmustine, Lomustine), inorganic ions (e.g., Cisplatin, Carboplatin), enzymes (e.g., Asparaginase), and hormones (e.g., Tamoxifen, Leuprolide, Flutamide, and Megestrol),among others. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is a common pathway agent, optionally caspase activators, apoptin, and survivin. The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is an agent that targets p53, p53 pathway members, IκB kinase (e.g., inhibitors or antagonists thereof), IKKβ, the proteasome / ubiquitin pathway (including the 20S proteasome), the PI3K / Akt pathway (such as mTOR). Exemplary apoptosis pathway agents also include, without limitation thereto, ONY-015, INGN201, PS1145, Bortezomib, CCI779, RAD-001, and antisense therapy targeting MDM2 (which is a regulator of p53 activity).ATTY. DOCKET NO.1143282.005213 The present disclosure also specifically describes therapeutic methods and compositions for use in such methods comprising the use of the high affinity clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and other high affinity clones disclosed infra in combination with another therapeutic agent, for treating cancers characterized by the expression of the (comprising core 2 O-glycans) prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, wherein the high affinity clone PB223 and other agent may be in the same or different compositions, and wherein the other agent is a direct cell killing agent, optionally a protein mixed lineage kinase domain like (MLKL), rapamycin (RAP) or derivatives and / or analogs thereof, such as everolimus or RAD001; CCI-779, ABT578, SAR543, vancomycin (an ethyl analog of FK506), AP23573, AP23841, KU-0063794, INK-128, EX2044, EX3855, EX7518, or compounds that bind to the ATP-binding cleft of mTOR, such as AZD08055 and OSIO27. The present disclosure also specifically describes combination therapies comprising the use of one of the inventive variants of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and exemplary other therapeutic agents which may elicit enhanced therapeutic efficacy compared to the individual therapeutic agents. Based thereon, lower dosages of said other therapeutic agent(s) can achieve the same therapeutic efficacy when used in combination with said one of the inventive variants of NEO-102 including the clone PB223, thereby allowing therapeutic benefit at a lower dosage which may decrease side-effects. The present disclosure also specifically describes a kit comprising said one of the inventive variants of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and one of said other agents. Typically said variant of NEO-102 including the clone PB223 and / or said other agent are provided at therapeutically effective dosages for the treatment of a disease or condition, e.g., variant MUC5AC (comprising core 2 O-glycans) expressing cancers, optionally cancer such as colorectal, pancreatic, ovarian, breast, uterine, lung, skin, or cervical cancer. The present disclosure also specifically describes pharmaceutical compositions which comprise a therapeutically effective amount of with one of the inventive variants ofATTY. DOCKET NO.1143282.005213 NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, formulated together with one or more pharmaceutically acceptable carriers and optionally one or more other active agents such as those above-identified. As used herein, the term "pharmaceutically acceptable carrier" means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), buccally, or as an oral or nasal spray. The present disclosure also specifically describes the use of inventive variants of NEO-102 including the clone PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, in combination with any of the anti-cancer antibodies disclosed in TABLE 1. The present disclosure also specifically describes a therapeutic method comprising administering an effective amount of affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, in combination with one or more chemotherapeutic agents such as oxaliplatin, irinotecan, topotecan, leucovorin, carmustine, vincristine, fluorouracil, streptozocin, and gemcitabine, and optionally one or more agents that target an apoptotic pathway (such as the common, extrinsic or intrinsic apoptotic pathway). The present disclosure also specifically describes a therapeutic method comprising administering an effective amount of an affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and optionally one or more agents that target an apoptotic pathway (such as the common, extrinsic or intrinsic apoptotic pathway) in combination with radiation therapy. Said antibody may or may not contain an Fc modification that increases ADCC or another effector function (e.g., as described above). In some embodiments said antibody in combination exhibits an enhanced or synergistic effect on treatment outcome relative to said antibody alone. Dosage forms In another aspect, the disclosure provides dosage forms comprising an affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, or a fragment thereof, and optionally another active suitable for in vivo use, e.g.,ATTY. DOCKET NO.1143282.005213 liquid dosage forms. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying agents, suspending agents, sweetening, flavoring, and perfuming agents. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. In order to prolong the effect of a drug, it may be desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non- irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppositoryATTY. DOCKET NO.1143282.005213 wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to the compounds of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons. Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium.ATTY. DOCKET NO.1143282.005213 Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel. According to the methods of treatment of the present invention, disorders are treated or prevented in a subject, such as a human or other animal, by administering to the subject a therapeutically effective amount of an affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, in such amounts and for such time as is necessary to achieve the desired result. The term "therapeutically effective amount" of a compound of the invention, as used herein, means a sufficient amount of the compound so as to decrease the symptoms of a disorder in a subject, generally a cancer characterized by expression of the MUC5AC variant (comprising core 2 O-glycans) bound by NEO-102. As is well understood in the medical arts a therapeutically effective amount of a compound of this invention will be at a reasonable benefit / risk ratio applicable to any medical treatment. In general, an affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, will be administered in therapeutically effective amounts via any of the usual and acceptable modes known in the art, either singly or in combination with one or more therapeutic agents. A therapeutically effective amount may vary widely depending on the severity of the disease, the age and relative health of the subject, the potency of the compound used and other factors. In general, satisfactory results are indicated to be obtained systemically at daily dosages of from about 0.03 to 2.5 mg / kg per body weight (0.05 to 4.5 mg / m2). An indicated daily dosage in the larger mammal, e.g. humans, is in the range from about 0.5 mg to about 100 mg, conveniently administered, e.g. in divided doses up to four times a day or in retard form. Suitable unit dosage forms for oral administration comprise from ca.1 to 50 mg active ingredient. In certain embodiments, a therapeutic amount or dose of an affinity variant of NEO-102, e.g., PB223 present invention may range from about 0.1 mg / kg to about 500 mg / kg (about 0.18 mg / m2to about 900 mg / m2), alternatively from about 1 to about 50 mg / kg (about 1.8 to about 90 mg / m2). In general, treatment regimens according to the present invention comprise administration to a patient in need of such treatment from about 10 mg to about 1000 mg of the compound(s) of this invention per day in single orATTY. DOCKET NO.1143282.005213 multiple doses. Therapeutic amounts or doses will also vary depending on route of administration, as well as the possibility of co-usage with other agents. In certain embodiments, a composition may comprise affinity variant of NEO- 102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and one or more agents that target an apoptotic pathway (such as the common, extrinsic or intrinsic apoptotic pathway), in amounts that exhibit an enhanced or synergistic effect relative to said antibody alone. Said enhanced or synergistic effect may be determined based on observable and / or measurable reduction in or absence of one or more of the following: reduction in the number of cancer cells or absence of the cancer cells; reduction in the tumor size; inhibition (i.e., slow to some extent and preferably stop) of cancer cell infiltration into peripheral organs including the spread of cancer into soft tissue and bone; inhibition (i.e., slow to some extent and preferably stop) of tumor metastasis; inhibition, to some extent, of tumor growth; and / or relief to some extent, one or more of the symptoms associated with the specific cancer; reduced morbidity and mortality, and improvement in quality of life issues. Upon improvement of a subject's condition, a maintenance dose of an affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, or a composition or combination of this affinity variant and another active agent (e.g., one of the active agents afore-mentioned) may be administered, if necessary. Subsequently, the dosage or frequency of administration, or both, may be reduced, as a function of the symptoms, to a level at which the improved condition is retained when the symptoms have been alleviated to the desired level, treatment should cease. The subject may, however, require intermittent treatment on a long-term basis upon any recurrence of disease symptoms. It will be understood, however, that the total daily usage of the affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and compositions containing same of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific inhibitory dose for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of theATTY. DOCKET NO.1143282.005213 patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. The invention also provides for a pharmaceutical combinations, e.g. a kit, comprising a) an affinity variant of NEO-102, e.g., PB223 as disclosed herein, in free form or in pharmaceutically acceptable salt form, and b) at least one co-agent. The kit can comprise instructions for its administration to a subject suffering from or susceptible to a disease or disorder. The terms "co-administration" or "combined administration" or the like as utilized herein are meant to encompass administration of the selected therapeutic agents to a single patient, and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time. The term "pharmaceutical combination" as used herein means a product that results from the mixing or combining of more than one active ingredient and includes both fixed and non-fixed combinations of the active ingredients. The term "fixed combination" means that the active ingredients, e.g., a compound of the invention and a co-agent, are both administered to a patient simultaneously in the form of a single entity or dosage. The term "non-fixed combination" means that the active ingredients, e.g., a compound of the invention and a co-agent, are both administered to a patient as separate entities either simultaneously, concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the two compounds in the body of the patient. The latter also applies to cocktail therapy, e.g., the administration of three or more active ingredients. Some examples of materials which can serve as pharmaceutically acceptable carriers include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, or potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, polyacrylates, waxes,ATTY. DOCKET NO.1143282.005213 polyethylene-polyoxypropylene-block polymers, wool fat, sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes, oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols; such a propylene glycol or polyethylene glycol; esters such as ethyl oleate and ethyl laurate, agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water, isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The agents or salts thereof may be formulated into pharmaceutical compositions for administration to animals or humans. These pharmaceutical compositions, which comprise an amount of the protein inhibitor effective to treat or prevent a cancer and a pharmaceutically acceptable carrier, are another embodiment of the present invention. These pharmaceutical compositions may be used in combination with other cancer treatments such as radiation therapy (also referred to as radiotherapy). This radiation can have an electromagnetic form, such as a high-energy photon, or a particulate form, such as an electron, proton, neutron, or alpha particle. A common form of radiation used in practice today is high-energy photons. Photon absorption in human tissue is determined by the energy of the radiation, as well as the atomic structure of the tissue in question. The basic unit of energy used in radiation oncology is the electron volt (eV); 10^3 eV=1 keV, 10^6 eV=1 MeV. Three interactions can be involved in photon absorption in tissue: the photoelectric effect, Compton effect, and pair production. Additionally provided are diagnostic methods comprising administering said affinity variant of NEO-102, e.g., PB223 to a patient and detecting the binding of said antibody to tumor cells in said patient. Exemplary embodiments of the invention provide compositions comprising said affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, (such as therapeutic compositions or diagnostic compositions), whichATTY. DOCKET NO.1143282.005213 compositions may comprise a pharmaceutically acceptable carrier, and additionally may comprise one or more additional therapeutic agents, such as another anti-cancer agent. Further exemplary embodiments of the invention provide nucleic acids encoding said affinity variant of NEO-102, e.g., PB223. Additionally provided are cells (such as mammalian, prokaryotic, yeast, or other eukaryotic cells) or vectors comprising a nucleic acid encoding said affinity variant of NEO-102, e.g., PB223. Additional exemplary embodiments of the invention provide methods of making said affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, comprising expressing a nucleic acid encoding said affinity variant of NEO- 102. In another aspect, this disclosure provides methods of detecting a cancer cell that expresses the antigen bound by PB223. Detecting the expression of cancer-associated antigen using affinity variant of NEO-102, e.g., PB223, that binds to an aberrantly glycosylated variant of MUC5AC (comprising core 2 O-glycans) may be used for diagnosis and staging of cancers (e.g., in radioimaging). For example, the level or extent of expression of (comprising core 2 O-glycans) antigens may indicate the stage of cancer, may be correlated with patient outcome, or may be predictive of the outcome of different treatment options. Currently, depending on the stage of the cancer, cancer treatment involves one or a combination of the following therapies: surgery to remove the cancerous tissue, radiation therapy, and chemotherapy. Detection of cancer cells using an affinity variant of NEO-102 can be used in conjunction with one or more therapies. Therapy may be targeted to the cancer cells thereby promoting effective treatment and / or reducing the effect on normal non-cancerous tissue. For example, cells expressing MUC5AC antigen (comprising core 2 O-glycans) may be targeted using radiotherapy, surgery, and / or cryotherapy. The therapeutic course (e.g., regimen and dosages of radiotherapy, surgical plan, or course of cryotherapy) that are therapeutically effective will depend on the particular cancer being treated, the extent of the disease and other factors familiar to the physician of skill in the art and can be determined by the physician.ATTY. DOCKET NO.1143282.005213 Expression of a cancer-associated antigen (such as MUC5AC (comprising core 2 O-glycans)) may be evaluated using an in vivo diagnostic assay, e.g., by administering an affinity variant of NEO-102, e.g., PB223, which binds the molecule to be detected and is tagged with a detectable label (e.g., a radioactive isotope or a fluorescent label) and externally scanning the patient for localization of the label. For example, one may expose cells within the body of the patient to an antibody which is optionally labeled with a detectable label, e.g., a radioactive isotope, and binding of the antibody to cells in the patient can be evaluated, e.g., by external scanning for radioactivity or by analyzing a biopsy taken from a patient previously exposed to the antibody. Aside from the above assays, various in vivo and in vitro assays for detecting the presence of a cancer-associated antigen are available to the skilled practitioner. The cancer-associated antigen (such as MUC5AC antigen (comprising core 2 O- glycans)) may be present on the cell surface. Alternatively or in addition the cancer- associated antigen (or a precursor thereof) may be produced and secreted at detectable levels. For example, the MUC5AC antigen (comprising core 2 O-glycans) may be detected in a biological fluid such as serum, e.g., using antibody-based assays (see also, e.g., U.S. Pat. No.4,933,294 issued Jun.12, 1990; WO91 / 05264 published Apr.18, 1991; U.S. Pat. No. 5,401,638 issued Mar.28, 1995; and Sias et al., J. Immunol. Methods 132:73-80 (1990)). The inventive affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, may also be used for purification or immunoprecipitation of the cancer-associated antigen from cells or other samples, for detection and quantitation of cancer-associated antigen in vitro, e.g., in an ELISA or a Western blot, to kill and eliminate cancer-associated antigen-expressing cells from a population of mixed cells, e.g., as a step in the purification of other cells. In another aspect, the invention provides a diagnostic kit comprising an affinity variant of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7. In one embodiment, the antibody may be directly or indirectly fixed to a solid phase support, such as a bead, plate, matrix, polymer, test tube, sheet, culture dish, or test strip. In another embodiment, the solid support may be an array. The inventive affinity variants of NEO-102 may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, aATTY. DOCKET NO.1143282.005213 maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The affinity variant of NEO-102, e.g., PB223 may optionally be produced in mammalian cells (such as CHO cells), bacterial cells, yeast cells, or other cells or using cell- free methods as known in the art. For diagnostic purposes, the affinity variant of NEO-102, e.g., PB223 of the present invention optionally may be detectably labeled, attached to a solid support, or the like. For example, the antibody may be labeled by conjugation to a radiolabel such as 111In or 86Y. In yet another embodiment, the invention concerns an article of manufacture comprising a container and a composition of matter contained within the container, wherein the composition of matter may comprise an affinity variant of NEO-102, e.g., PB223. The article may further optionally comprise a label affixed to the container, or a package insert included with the container, that refers to the use of the composition of matter for the therapeutic treatment or diagnostic detection of a (comprising core 2 O- glycans) antigen expressing tumor. Another embodiment of the present invention is directed to a method for inhibiting the growth of a cell that expresses a cancer-associated antigen as described herein (such as MUC5AC (comprising core 2 O-glycans)), wherein the method comprises contacting the cell with an affinity variant of NEO-102, e.g., PB223 that binds to the cancer- associated antigen and with one or more agents that target an apoptotic pathway (such as the common, extrinsic or intrinsic apoptotic pathway), and wherein the binding of the antibody to the cancer-associated antigen causes inhibition of the growth of the cell expressing the cancer-associated antigen. In preferred embodiments, the cell is a MUC5AC (comprising core 2 O-glycans) expressing cancer cell and binding of the antibody to the cancer-associated antigen causes death of the cell expressing the cancer-associated antigen. Such antibodies may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The antibodies employed in the methods of the present invention may optionally be produced in CHO cells or bacterial cells.ATTY. DOCKET NO.1143282.005213 Yet another embodiment of the present invention is directed to a method of therapeutically treating a mammal having a cancerous tumor comprising cells that express a cancer-associated antigen as described herein (MUC5AC antigen (comprising core 2 O- glycans)), wherein the method comprises administering to the mammal a therapeutically effective amount of an affinity variant of NEO-102, e.g., PB223 that binds to the cancer- associated antigen and one or more agents that target an apoptotic pathway (such as the common, extrinsic or intrinsic apoptotic pathway), thereby resulting in the effective therapeutic treatment of the tumor. Antibodies employed in the methods of the present invention may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The antibodies employed in the methods of the present invention may optionally be produced in mammalian cells, e.g., CHO cells, yeast cells, insect cells or bacterial cells. Yet another embodiment of the present invention is directed to a method of determining the presence of a cancer-associated antigen as described herein (such as MUC5AC, antigen (comprising core 2 O-glycans)) in a sample suspected of containing the cancer-associated antigen, wherein the method comprises exposing the sample to an affinity variant of NEO-102, e.g., PB223 that binds to the cancer-associated antigen and determining binding of the antibody to the cancer-associated antigen in the sample, wherein the presence of such binding is indicative of the presence of the cancer-associated antigen in the sample. Optionally, the sample may contain cells (which may be cancer cells) suspected of expressing the cancer-associated antigen. The affinity variant of NEO-102, e.g., PB223 employed in the method may optionally be detectably labeled, attached to a solid support, or the like. A further embodiment of the present invention is directed to a method of diagnosing the presence of a tumor in a mammal, wherein the method comprises detecting the level of expression of a cancer-associated antigen (a) in a test sample of tissue cells obtained from said mammal, and (b) in a control sample of known normal non-cancerous cells of the same tissue origin or type, wherein a higher level of expression of the cancer- associated antigen in the test sample, as compared to the control sample, is indicative of the presence of tumor in the mammal from which the test sample was obtained.ATTY. DOCKET NO.1143282.005213 Another embodiment of the present invention is directed to a method of diagnosing the presence of a tumor in a mammal, wherein the method comprises (a) contacting a test sample comprising tissue cells obtained from the mammal with an inventive antibody that binds to MUC5AC (comprising core 2 O-glycans) and (b) detecting the formation of a complex between the antibody and the MUC5AC (comprising core 2 O- glycans) in the test sample, wherein the formation of a complex is indicative of the presence of a tumor in the mammal. Optionally, the antibody employed is detectably labeled, attached to a solid support, or the like, and / or the test sample of tissue cells is obtained from an individual suspected of having a cancerous tumor. Yet another embodiment of the present invention is directed to a method of binding an antibody to a cell that expresses a MUC5AC (comprising core 2 O-glycans), wherein the method comprises contacting a cell that expresses a cancer-associated antigen with said antibody under conditions which are suitable for binding of the antibody to said cancer-associated antigen and allowing binding therebetween. In preferred embodiments, the antibody is labeled with a molecule or compound that is useful for qualitatively and / or quantitatively determining the location and / or amount of binding of the antibody to the cell. Except where otherwise provided the techniques and procedures are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification. See, e.g., Sambrook, et al (2001) “Molecular Cloning: A Laboratory Manual [3rd Ed] Cold Spring Harbor Laboratory Press”. Standard techniques may be used for recombinant DNA, oligonucleotide synthesis, and tissue culture, and transformation (e.g., electroporation, lipofection). Enzymatic reactions and purification techniques may be performed according to manufacturer's specifications or as commonly accomplished in the art or as described herein. The nomenclatures utilized in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art. Standard techniques may be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients.ATTY. DOCKET NO.1143282.005213 Diagnostic Methods The subject affinity variants of NEO-102, and antigen-binding fragments thereof may be used in diagnostic methods for detecting the presence or absence of a MUC5AC antigen (comprising core 2 O-glycans). The affinity variants of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, which selectively bind the MUC5AC antigen (comprising core 2 O-glycans), and antigen-binding fragments thereof, may be used in methods comprising (a) contacting a test sample with an affinity variant of NEO-102, e.g., PB223, or fragment thereof, and (b) assaying for antibody-epitope complexes, wherein the presence of said epitope is indicative of a carcinoma. Further, the affinity variants of NEO-102, e.g., PB223 and fragments thereof which selectively bind MUC5AC antigen (comprising core 2 O-glycans), may be used in a method for detecting the presence of a MUC5AC epitope (comprising core 2 O-glycans), comprising (a) administering to said patient a labeled affinity variants of NEO-102, e.g., PB223, or fragment thereof, that binds a MUC5AC epitope (comprising core 2 O-glycans), and (b) detecting the presence of a MUC5AC epitope (comprising core 2 O-glycans); wherein the presence of said epitope is indicative of a carcinoma. The antibody-epitope complex may be detected by Western blot, radioimmunoassay, ELISA (enzyme linked immunosorbent assay), "sandwich" immunoassay, immunoprecipitation assay, precipitation reaction, gel diffusion precipitation reaction, immunodiffusion assay, agglutination assay, complement-fixation assay, immunohistochemical assay, fluorescent immunoassay, and protein A immunoassay. The sample may be sample is a tissue biopsy, lymph, urine, cerebrospinal fluid, amniotic fluid, inflammatory exudate, blood, serum, stool, or liquid collected from the colorectal tract. The subject affinity variants of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and fragments thereof which selectively bind to a variant MUC5AC antigen (comprising core 2 O-glycans), and antigen-binding fragments thereof may be used in diagnostic methods for detecting the presence or absence of said variant MUC5AC antigen (comprising core 2 O-glycans), wherein the presence of the antigen is indicative of cancer including but not limited to prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, .ATTY. DOCKET NO.1143282.005213 The diagnostic methods may be used with patients at risk of cancer or patients without symptoms. The subject affinity variants of NEO-102, e.g., PB223 comprising the VH and VL sequences shown in FIG.6 and FIG.7, and fragments thereof which selectively bind to a variant MUC5AC antigen (comprising core 2 O-glycans), and antigen-binding fragments thereof may be recombinant. The fragments of antibodies which selectively bind a variant MUC5AC antigen (comprising core 2 O-glycans) include a Fab, Fab', F(ab')2, Fv, CDR, paratope, or portion of the subject affinity variants of NEO-102, e.g., PB223 that is capable of binding the antigen. These antibodies may be chimeric, humanized, anti-idiotypic, single- chain, bifunctional, or co-specific. The antibodies further may be or fragment is conjugated to a label, including but not limited to a chemiluminescent label, paramagnetic label (e.g., aluminum, manganese, platinum, oxygen, lanthanum, lutetium, scandium, yttrium, or gallium), an MRI contrast agent, fluorescent label, bioluminescent label, or radioactive label. Additionally, these antibodies and fragments thereof may be attached to a solid support (e.g., bead, test tube, sheet, culture dish, or test strip) such as an array. These methods may be used to detect colorectal polyps. The method may further comprise additional testing for the presence of tumors including but not limited to benign tumors, malignant tumors, metastatic tumors, and non-metastatic tumors. For example, the diagnostic method may detect pre-cancerous cells that express a cell marker comprising a MUC5AC antigen (comprising core 2 O-glycans). The method may comprise imaging a MUC5AC epitope (comprising core 2 O- glycans) bound by NEO-102 by positron emission tomography (PET), CCD low-light monitoring system, x-ray, CT scanning, scintigraphy, photo acoustic imaging, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, paramagnetic imaging, and endoscopic optical coherence tomography. The MUC5AC antigen (comprising core 2 O-glycans) bound by the subject affinity variants of NEO-102 may be used as a cancer biomarker. Detection of the variant MUC5AC antigen (comprising core 2 O-glycans) in a biological sample, such as a subject's serum, biopsied neoplastic cells or fecal sample, may be performed by means using the subject affinity variants of NEO-102. For example, a biological sample (e.g., a tumor, serum or fecalATTY. DOCKET NO.1143282.005213 sample) is obtained from a subject, then MUC5AC antigen (comprising core 2 O-glycans) is measured (e.g., by ELISA or PCR), and compared with corresponding samples from normal subjects. Measuring methods include any method of nucleic acid detection, for example in situ hybridization using antisense DNA or cRNA oligonucleotide probes, ultra-high throughput sequencing, nanostring technology, microarrays, rolling circle amplification, proximity-mediated ligation, PCR, qRT-PCR ChIP, ChIP-qPCR, or MUC5AC antigen (comprising core 2 O-glycans)-binding antibodies. Comparatively high levels of the variant MUC5AC antigen (comprising core 2 O-glycans) bound by NEO-102 and by the inventive affinity variants thereof indicate the presence and / or severity of a cancer characterized by expression of the variant MUC5AC antigen (comprising core 2 O-glycans), and may indicate metastasis or poor cancer prognosis. The inventive affinity variants of NEO-102 such as PB223 which selectively bind a variant MUC5AC antigen (comprising core 2 O-glycans) correlated with different cancers, and antigen-binding fragments thereof, may be used in SQUID (Superconducting Quantum Interference Device) techniques for diagnostic methods. The SQUID technique comprises attaching nanoparticles of iron oxide to antibodies, which are then injected into the patient. If a tumor is present, the antibodies with conjugated nanoparticles recognize and bind to the variant MUC5AC antigen (comprising core 2 O-glycans) expressed on tumor cells. See, e.g., Hao, et al. (2010) Journal of Physics 43: 474004. In a SQUID method, the patient is then surrounded with sensitive magnetic coils in a superconducting quantum interference device (SQUID). A magnetic field is generated and all of the metal nanoparticles align in one direction. When the magnetic field is broken, the nanoparticles emit an electromagnetic signal as they relax back into their original state. By measuring the strength of the signal, one may tell how many metal particles, and therefore how many tumor cells, may be present, and where in the patient the tumor cells are located. See, e.g., Shao, et al. (2010) Beilstein, Journal of Nanotechnology 1: 142-154. Samples and Procurement of Samples The samples used in the methods described herein may be taken from a subject (patient) include but are not limited to a body fluid or secretion including but not limited to blood, serum, urine, plasma, prostatic fluid, seminal fluid, semen, the external secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, cerebrospinal fluid, sputum,ATTY. DOCKET NO.1143282.005213 saliva, milk, peritoneal fluid, pleural fluid, cyst fluid, secretions of the breast ductal system (and / or lavage thereof), broncho alveolar lavage, lavage of the reproductive system and lavage of any other part of the body or system in the body; samples of any organ including isolated cell(s) or tissue(s), wherein the cell or tissue can be obtained from an organ selected from, but not limited to lung, colon, ovarian, uterine, cervical, and / or breast tissue; stool or a tissue sample, or any combination thereof. In some embodiments, the term encompasses samples of in vivo cell culture constituents. Prior to be subjected to the diagnostic assay, the sample can optionally be diluted with a suitable diluent. Numerous well known tissue or fluid collection methods can be utilized to collect the biological sample from the subject in order to determine the level of DNA, RNA and / or polypeptide of the marker of interest in the subject. Examples of tissue or fluid collection methods include, but are not limited to, fine needle biopsy, needle biopsy, core needle biopsy and surgical biopsy (e.g., brain biopsy), and lavage. Regardless of the procedure employed, once a biopsy / sample is obtained the level of the marker may be determined and a diagnosis can thus be made. Detection of Antigens recognized by NEO-102 The invention also provides a method for detecting the variant MUC5AC antigen (comprising core 2 O-glycans) bound by NEO-102 and its affinity variants disclosed herein in a biological sample, comprising: contacting a biological sample with an affinity clone according to the present invention and detecting said interaction; wherein the presence of an interaction correlates with the presence of a variant MUC5AC antigen (comprising core 2 O-glycans) in the biological sample. The present invention also provides methods, uses, devices and assays for the diagnosis of cancers such as non-solid and solid tumors, cancer of the breast, prostate, lung, ovary, colon, uterus, stomach, cervix, liver, pancreas, and wherein the cancer may be invasive or metastatic. Optionally a plurality of markers may be used with the present invention. The plurality of markers may optionally include a markers described herein, and / or one or more known markers. The plurality of markers is preferably then correlated with the disease or condition. For example, such correlation may optionally comprise determining the concentration of each of the plurality of markers, and individually comparing each marker concentration to a threshold level. Optionally, if the markerATTY. DOCKET NO.1143282.005213 concentration is above or below the threshold level (depending upon the marker and / or the diagnostic test being performed), the marker concentration correlates with the disease or condition. Optionally and preferably, a plurality of marker concentrations correlates with the disease or condition. Additionally, the MUC5AC antigens (comprising core 2 O-glycans) may be used as specific biomarkers for pancreas and colon cancer, and can be measured in biopsied tissue as well as in subject serum and fecal samples, as described herein. Additionally, diagnostic procedures used to detect colorectal cancer including but not limited to fecal occult blood test (FOBT), colonoscopy, computed tomographic colonography (virtual colonoscopy) [detects colorectal lesions larger than 6 mm in diameter with the same sensitivity as colonoscopy], flexible sigmoidoscopy, double-contrast barium enema, and digital rectal examination. Winawer, et al. (1997) Am J. Gastroenterology 112: 594-642; Blum (1995) Eur. J. Canc.31: 1369-72; Ransohoff & Sandler (2002) N. Engl. J. Med.346: 34611; Bruzzi (2002) N. Engl. J. Med.346: 1672-74; and Laghi, et al. (2002) Am. J. Surg.183: 124-31. Immunoassays The subject affinity variants of NEO-102 and binding fragments thereof, may be used in immunoassays to qualitatively or quantitatively detect and analyze markers in a sample. This method comprises providing an antibody specifically binds to the variant MUC5AC antigen (comprising core 2 O-glycans) bound by NEO-102; contacting a sample with the antibody; and detecting the presence of a complex of the antibody bound to the marker in the sample. The MUC5AC antigen (comprising core 2 O-glycans) bound by the NEO-102 antibody and its affinity variants may be detected and / or quantified using any of a number of well recognized immunological binding assays. Useful assays include, for example, an enzyme immune assay (EIA) such as enzyme-linked immunosorbent assay (ELISA), a radioimmunoassay (RIA), a Western blot assay, or a slot blot assay. See, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168. Optionally, the NEO-102 antibody or one of its affinity variants can be fixed to a solid support to facilitate washing and subsequent isolation of the complex, prior to contacting the antibody with a sample. Examples of solid supports include but are notATTY. DOCKET NO.1143282.005213 limited to glass or plastic in the form of, e.g., a microtiter plate, a stick, a bead, or a microbead. Antibodies may be attached to a solid support. After incubating the sample with antibodies, the mixture is washed and the antibody-marker complex formed may be detected. This can be accomplished by incubating the washed mixture with a detection reagent. Alternatively, the marker in the sample can be detected using an indirect assay, wherein, for example, a second, labeled antibody is used to detect bound marker-specific antibody, and / or in a competition or inhibition assay wherein, for example, a monoclonal antibody which binds to a distinct epitope of the marker are incubated simultaneously with the mixture. Throughout the assays, incubation and / or washing steps may be required after each combination of reagents. Incubation steps can vary from about 5 seconds to several hours, preferably from about 5 minutes to about 24 hours. However, the incubation time will depend upon the assay format, marker, volume of solution, concentrations. Usually the assays will be carried out at ambient temperature, although they can be conducted over a range of temperatures (e.g., 10 degrees C.-40 degrees C.). The immunoassay can be used to determine a test amount of a marker in a sample from a subject. First, a test amount of a marker in a sample may be detected using the immunoassay methods described above. If a marker is present in the sample, it will form an antibody-marker complex with an antibody specifically binds the marker under suitable incubation conditions described above. The amount of an antibody-marker complex can optionally be determined by comparing to a standard. As noted above, the test amount of marker need not be measured in absolute units, as long as the unit of measurement can be compared to a control amount and / or signal. Such immunoassays are known in the art and include but not limited to radio-immunoassay (RIA), enzyme linked immunosorbent assay (ELISA), magnetic immunoassay, immunoblot, Western blot, immunoprecipitation assays, immunohistochemical analysis, and fluorescence activated cell sorting (FACS). See Wild, (2008) [Ed.] The Immunoassay Handbook [3rd Ed.] Elsevier. Radio-Imaging Methods The MUC5AC antigen (comprising core 2 O-glycans) bound by the NEO-102 antibody and its affinity variants and antigen-binding fragments thereof, may be used inATTY. DOCKET NO.1143282.005213 radio-imaging methods to diagnosis MUC5AC (comprising core 2 O-glycans) expressing cancers, including e.g., prostate cancers, skin cancers (e.g., melanoma), ovarian cancers, cervical cancers, uterine cancers, , or to monitor the progression of MUC5AC antigen (comprising core 2 O-glycans) expressing tumors. These methods include but are not limited to, positron emission tomography (PET) single photon emission computed tomography (SPECT). Both of these techniques are non-invasive, and can be used to detect and / or measure a wide variety of tissue events and / or functions, such as detecting cancerous cells for example. SPECT may optionally be used with two labels simultaneously. See U.S. Pat. No.6,696,686. In order that the invention herein described may be fully understood, the above detailed description is set forth. Various embodiments of the invention are described in detail and may be further illustrated by the provided examples. The examples provided are intended to be illustrative, rather than limiting, on the scope of the invention, which is limited only by the scope of the claims provided after the examples. EXAMPLES EXAMPLE 1: Methods Used For Affinity Maturation of NEO-102 TABLE 2: NEO-102 Ab (Ensituximab) Help Name Ensituximab (USAN / INN) N SATTY. DOCKET NO.1143282.005213 LTCLVKGFYP SDIAVEWESN GQPENNYKTM PPVLDSDGSF FLYSKLTVDK SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK R 5-As discussed above, Applicant’s goal was to engineer the VH and VL sequences of the NEO-102 sequence (See VH and VL sequences of NEO-102 in TABLE 2 and FIG.7) through Fast Screening for expression biophysical properties and affinity (FASEBA) designed to maintain the binding to the target MUC5AC antigen (comprising core 2 O-glycans) but to obtain novel clones with increased affinity to the target antigen, i.e., possessing h a higher KD. This procedure included performing PML (Precise mutagenesis library) construction in FASEBA format and comprised mutagenesis of each of the residues of the VH and VL residues of NEO-102. The library was constructed using saturation mutagenesis into all residues in the VH and VL regions of the antibody. Each targeted codon was mutated into the other 19 amino acid excluding the wild type. Next generation sequencing (NGS) was employed to check the distribution of the Precise Mutagenesis Library (PML). FIG.6 contains the VH and VL amino acid sequences of a preferred high affinity clone (referred to as PB223) having the sequences further disclosed in TABLE 3 in the following example. This high affinity clone contains substitutions in both the VH and VL regions (in relation to the wild-type NEO-102 VH and VL sequences) and moreover contains modifications in both the CDRs and framework residues of NEO-102. PB223 which comprises the VH and VL amino acid sequences shown FIG.6 and FIG.7, contains a total of 5 modifications (relative to NEO-102 or Ensituximab): (1) VH (framework) residue 28, i.e., (S→E), (2) VH (CDR) residue 35 (in VH CDR1), i.e., (N→I),ATTY. DOCKET NO.1143282.005213 (3) VH (CDR) residue 58 (in VH CDR2), i.e., (S→V), (4) VH (CDR) residue 62 (also in the VH CDR2), i.e., (G→K); and (v) further comprises a VL modificaƟon at VL (CDR) residue 54 (in the VL CDR2), i.e., (A→G). TABLE 3: Affinity maturation using FASEBA screening for high affinity clones. Sequence Ka Kd(1 / s) KD Ratio Ratio 28 35 58 61 62 54 ID (1 / Ms) (M) (kd) (kD) S N S S G A - G - G - - - - - - - - -ATTY. DOCKET NO.1143282.005213 AHF- 1.13E+05 4.36E- 3.87E- 1.37 1.68 E I V L K - 18098 04 09 -VH (framework) residue 28, i.e., (S→E), a modified VH (CDR1) residue 35 (N→I), and a modified VH (CDR2) residue 62 (G→K). Clone , further comprises the (S→V) modificaƟon at VH (CDR2) residue 58. By contrast, in relaƟon to lacks a VL modification of (A→G) at posiƟon 54. Clone comprises a (S→L) modificaƟon at VH (CDR2) residue 61 and lacks the (S→V) modificaƟon at VH (CDR2) residue 58. FIG.6 contains the VH and VL sequences of PB223. In the Figure the CDR residues are in red and the mutated residues are underlined. FIG.7 contains an alignment of the VH and VL sequences of NEO-102 and PB223. In the FIG. the CDR residues are in red fontATTY. DOCKET NO.1143282.005213 and the mutated residues in the CDRs and in the frameworks are underlined and green font. From these Figures it can be seen that NEO102m (PB223) comprises mutated residues in both the CDRs and framework residues. Again, as was previously noted, b EXAMPLE 3: TABLE 4 TABLE 4: Flow cytometry analysis of NEO-102 and PB223 binding to different cancer cell lines. CELL LINE TUMOR TYPE NEO-102PB223 STAININGSTAININGATTY. DOCKET NO.1143282.005213 Malignant 24.66% 43.12% OV90 Papillary SerousATTY. DOCKET NO.1143282.005213 Array data: The microarray data obtained using these methods and materials is contained in FIG.3 and FIG.4 and was analyzed using Mapix software (Innopsys). The data revealed that PB223 binds to O-glycans terminated with a (2,6) sialic acids. This includes both sTn antigens (03 and 04), and truncated Core-2 O-glycan structures (030, 053 and 083) at 20µg / mL. At lower concentrations PB223 weakly binds to the 03 and 04 O-glycans at 10µg / mL and 2µg / mL (See FIG.3 and FIG.4). Based on these results, we concluded that PB223 binds strongly to the truncated Core-2 O-glycans (see FIG.5 which contains the structures of different O-glycans including Core 2 O-glycans.) More specifically the microarray data contained in FIG.3, which was analyzed using Mapix software (Innopsys) was based on binding experiments using PB223 screened against the O-glycan microarray of FIG.1 which comprises the O-glycan structures in revealed that PB223 binds to O-glycans which are terminated with α (2,6) sialic acids, which glycan group includes both sTn antigens (03 and 04) as well as other O-glycans (030, 053, and 083). Further, the microarray data contained in FIG.4, analogously was analyzed using Mapix software (Innopsys). In these experiments the antibody (PB223) concentration was 10 µg / mL or 2 µg / mL. The results revealed that the anti-human IgG Fc region (Cy3) does not interact with any of the O-glycans in the O-glycan array of FIG.1. As is disclosed in the following examples, the inventors conducted a further comprehensive characterization of mAb PB223, elucidating its keys properties, in particular those which corroborate its potential efficacy for treatment of different types of cancers. These experiments and the results thereof are disclosed in the following examples. This further investigation included an assessment of PB223’s internalization into OV-90 cells (ovarian cancer cell line reactive with PB223 in flow cytometry), its binding to specific solid human tumors and to normal human tissues and other properties significant to its potential usage as a cancer therapeutic agent.ATTY. DOCKET NO.1143282.005213 MATERIALS AND METHODS For the FACS binding assay, target cells were harvested by centrifugation and then resuspended in FACS buffer. Next, the cell density was adjusted as needed and the cell suspension was transferred into the assay plate. Then, the samples’ working solution was added to the plate and the plate was incubated at 4oC for 1 hour. Once incubation was completed, the assay plate was centrifugated, and the supernatant was discarded. After centrifugation, the cell pellet was resuspended in working solution containing the detection antibody, and the assay plate was incubated at 4oC for 20 minutes in the dark. Afterward, cells in the assay plate were washed with FACS buffer, and then the assay plate was examined using the BD FACS Celesta flow cytometer. RESULTS Flow cytometry analysis revealed strong binding of Herceptin to SK-BR-3 cells (human breast cancer cell line) (FIG.8) while PB223 exhibited strong binding to the OV-90 cells (FIG.9). Internalization Assay Using MATERIALS AND METHODS Target cells (OV-90 and SK-BR-3) were maintained with corresponding complete culture medium at 37 °C with 5% CO2. Before proceeding with the internalization assay, target cells were profiled by flow cytometry as disclosed supra to assess their binding to PB223. A live cell image-based internalization assay was employed to observe the internalization process of the monoclonal antibody (mAb) PB223 (AHF18095) within the OV- 90 cell line. As validation measure, the interaction between the mAb Herceptin and its target cell SK-BR-3 was used as system control. Herceptin was used at 30 nm with a 2-fold dilution. In the experimental group, the OV-90 cell line served as target, and mAb AHF18095 was tested at concentrations ranging from 60 nM to 0.94 nM, with a 2-fold dilution. To ensure specificity,ATTY. DOCKET NO.1143282.005213 an anti-HEL human IgG1 was included as negative control. The response curve of the analysis was evaluated at 48 hours to analysis the internalization dynamics. For the internalization assay, cells were first digested with Accutase (a natural enzyme mixture with proteolytic and collagenolytic enzyme activity), then harvested by centrifugation and then resuspended in assay buffer (complete culture medium). After adjusting the target cell density, the target cell suspension was transferred to the assay plate according to the map schemes. The assay plate was then incubated in a cell incubator (37 °C with 5% CO2) overnight. The following day, target cells were incubated with working solutions containing Herceptin, PB223 and human IgG1 negative control for 15 minutes at 37 °C with 5% CO2to allow conjugation. Following this, images depicting internalization were captured at determined time points in Incucyte® Live-Cell Analysis System with an appropriate fluorescent module configured for the indicated time. Raw data and results were analyzed and exported with the Incucyte® Live-Cell Analysis System. For the internalization assay, the Incucyte human Fabfluor-pH antibody labeling Dye was used to streamline the labeling process efficiently. This dye is tailored to rapidly label Fc-containing antibodies with Fab fragment-conjugated pH-sensitive fluorophore. The pH sensitive dye-based system capitalizes on the acidic environment of the lysosomes to quantify internalization of the labeled antibody. In this process, Fabfluor-labeled antibodies utilized in this process, initially reside in the neutral extracellular solution (pH7.4) where they interact with cell surface specific antigens and are undergo internalization. Upon entry into the lysosomes, characterized by an acidic environment (pH4.5 to 5.5), there is a noticeable increase in fluorescence. In the absence of expression of the specific antigen, internalization does not occur, as determined by low fluorescence intensity of the labeled antibodies. To minimize background fluorescence, we utilized used the Incucyte integrated analysis software. Together with the Incucyte S3 Live-Cell Analysis System, the IncucyteATTY. DOCKET NO.1143282.005213 Fabfluor-pH antibody labeling dyes enable real-time, kinetic evaluation of antibody internalization. RESULTS Exemplary results of this internalization analysis are contained in FIG.10 and FIG. 11. The data therein illustrate the internalization dynamics of Herceptin and PB223 with their respective cell lines over various concentrations and time intervals. As is shown in FIG. 12, we observed that the system control, Herceptin, was internalized by SK-BR-3 cells (FIG. 12). FIG. 12 presents the dose-dependent responses of Herceptin with SK-BR-3 at 48 hours (system control). As further shown in FIG. 13 PB223, when incubated with OV-90 cells, elicited showed internalization effects after 48 hours (FIG.13). No internalization effect was observed with the isotype control antibody anti-HEL Human IgG1. More specifically, FIG.12 shows the dose-dependent responses of Herceptin with SK-BR-3 at 48 hours (system control). FIG. 13 analogously shows the dose-dependent responses for PB223 with OV-90 at the same time point. These results demonstrate that PB-233 significantly internalizes OV-90 cells after incubated therewith after 48 hours. By contrast, incubation of OV-90 cells with the isotype control antibody, anti-HEL human IgG1, did not elicit any observable internalization effects. O-glycan profiling of O-glycans reactive with PB223 and O-glycan profiling of O-glycans expressed by human cancer cell lines reactive with PB223 in flow cytometry An O-glycan array consisting of 94 O-glycans was used to identify the O-glycans that bind to PB223 as disclosed below. MATERIALS AND METHODS An O-glycan array consisting of 94 O-glycans was employed to identify the O- glycans that bind PB223. The array was blocked for 30 min using a Glycan Array BlockingATTY. DOCKET NO.1143282.005213 Buffer (GAAB, TBS-T based buffer). Then the array was washed 3 times using the GAAB). The samples were diluted in GAAB to the desired concentrations, and then applied directly to the array. The array was covered and shaken at 80 rpm for 1 h at room temperature. The array was then washed 3 times again with GAAB, and then PB223 was diluted in GAAB and used at three concentrations (20µg / mL, 10µg / mL and 2µg / mL) to incubate with the O-glycan Array for 1 h at room temperature covered from light and shaken at 80 rpm. The Arrays were then washed and incubated with anti-human IgG FcCy3 at a concentration of 20µg / mL for 1 h at room temperature covered from light and shaken at 80 rpm. The Arrays were then washed 3x with GAAB and 2x with MilliQ water. The array was then read using an Innopsys InnoScan 710 Microarray Scanner with a high-power laser at 5PMT. Software was used to detect each spot on the array and calculate the relative fluorescence units (RFU) intensity for each spot. Background RFU was subtracted from each spot’s RFU value. The median of each glycan’s spot was determined and graphed. OV-90 and HCC-1937 (human triple-negative breast cancer cell line) are reactive with PB223 in flow cytometry (FIG.14, 15), while the LOVO (human colorectal cancer cell line) does not react to PB223 in flow cytometry (FIG. 16). The O-glycan profiling procedure on human cancer cells involved several steps, encompassing N-glycan removal, O-glycan preparation, permethylation and MDS MALDI analysis as described below: N-glycans removal: After 3 washes in PBS the cell pellet was resuspended in 1 mL of lysis buffer (25 mM TRIS, 150mM NaCl, 5mM EDTA, 0.5% w / v CHAPS, pH 7.4) and sonicated (5 pulses of 10 s). The lysed sample was next dialyzed against 50 mM ammonium bicarbonate for 24 h at 4 °C and with the dialysis buffer changed three times. After lyophilization, the dialyzed material was resuspended in 1 mL of a 2 mg / mL DTT (1,4-Dithiothreitol) solution and incubated at 50 °C for 90 min. Then 0.5 mL of 12 mg / mL solution of iodoacetamide in 0.6 M TRIS buffer pH 8.5 was added to the DTT-treated sample and sample were incubated at room temperature in the dark for 90 min. Samples were then dialyzed against 50 mM ammonium bicarbonate at 4 °C for 16h-24h, changing the buffer 3 times. The molecular cut-off should be between 1 and 5 kDa. After dialysis samples were transferred into a 15 mL tubes and lyophilized.ATTY. DOCKET NO.1143282.005213 Dry samples were then resuspended in 0.5 mL of a 50 μg / mL solution of TPCK- treated trypsin in 50 mM ammonium bicarbonate and incubated overnight (12-16 h) at 37 °C. Reaction was stopped by adding 2 drops of 5% acetic acid. The trypsin-digested samples were then added onto a C18 Spe-Pak (50 mg) column with methanol, 5% acetic acid, 1-propanol and 5% acetic acid. Column was then washed with 4 ml of 5% acetic acid and peptides were eluted from the C18 column with 2 ml of 20% 1-propanol, then 2 ml 40% 1-propanol and finally 2 ml of 100% 1-propanol. All the eluted fractions were pooled, and samples were lyophilized. Dried samples were then resuspended thoughtfully in 200 μL of 50 mM ammonium bicarbonate and 2 μL of PNGaseF and incubated at 37 °C for 4 h. Then, another 3 μL of PNGaseF was added for overnight (12-16 h) incubation at 37 °C. Reaction was stopped by adding 2 drops of 5% acetic acid. The PNGaseF-digested sample were added onto a C18 Spe-Pak (50 mg) column with Methanol, 5% acetic acid, 1-Propanol and 5% acetic acid and the flow through was discarded. O-glycans preparation: The material bound to the column (containing peptides and potentially O- glycopeptides) was collected by sequential elutions with 1 mL of 20% 1-propanol, 1 mL of 40% 1-propanol and 1 mL of 100% 1-propanol. The eluted fractions were then lyophilized.400 μL of a 55 mg / mL NaBH4 (sodium borohydride) in 0.1 M NaOH solution were then added to the samples and samples were incubated at 45 °C overnight. The reaction was terminated by adding 3-4 drops of pure (100%) acetic acid until fizzing stops. The acetic acid-neutralized samples were loaded onto a Dowex (50W X8, mesh size 200-400) ion exchange resin column previously washed with 10 ml of 5% acetic acid. After loading the column was then washed with 3 mL of 5% acetic acid. Flow through was then collected, and pooled. The collected material was lyophilized.1 mL of acetic acid: methanol solution (1:9; v / v=10%) was then added to the lyophilized sample. Samples were then vortexed thoroughly and dried under a stream of nitrogen for three times.ATTY. DOCKET NO.1143282.005213 The co-evaporated dried samples were then resuspended in 200 μL of 50% methanol and loaded onto a C18 Spe-Pak (50 mg) column conditioned with methanol, 5% acetic acid, 1-propanol and 5% acetic acid. After loading the column was washed with 4 mL of 5% acetic acid and flow through was collected and pooled. The collected material was lyophilized before to proceed to permethylation. Permethylation: The Preparation of the slurry NaOH / DMSO solution is made fresh every time. Mortar, pestle, and glass tubes were washed with Milli Q water and dried beforehand. Whenever possible, liquid reagents were handled with disposable glass pipettes. Solvents are HPLC grade or higher. 7 pellets of NaOH were grinded with a clean and dry mortar and pestle in 3 mL of DMSO.1 mL of this slurry solution was added to dry sample in a glass tube with a screw cap. Then, 500 μL of Iodomethane were added, the lid was closed tightly, and the sample was shaken at room temperature for ~30 min. Then, the cap was open slowly as gas pressure has built up and 1 mL of MilliQ water was added to stop the reaction. Tube was vortexed until all solid is dissolved. Then, 1 mL of Chloroform and additional 3 mL of MilliQ water were added, tubes were vortexed thoroughly to mix both phases and centrifuged briefly to separate the chloroform and the water phases (~5000 rpm, <20 sec). The aqueous top layer was discarded, and the wash was repeated 2 more times adding 3 ml of Milli Q water. The chloroform fraction was dried with a SpeedVac (~20-30 min). Then, the dried sample were resuspended with 200 μL of 50% methanol and loaded onto a C18 Spe-Pak (200 mg) column conditioned with Methanol, Acetonitrile and MilliQ water. After loading, the column was washed with 2 mL of 15% acetonitrile and then the column was eluted in a clean glass tube with 3 mL of 50% acetonitrile. The eluted fractions were then lyophilized for MS analysis. MS MALDI analysis: For the MS analysis, samples were run by PCG-LC-MS / MS on a Thermo Fisher Altis Triple Quad Mass Spectrometer. MS1 data was deconvoluted and analyzed using GlycoWorkBench 2.0 and manual interpretation. Reflective positive mode was used, andATTY. DOCKET NO.1143282.005213 data were recorded between 500 m / z and 4000 m / z for O-glycans. For each MS O-glycan profiles the aggregation of 20,000 laser shots or more were considered for data extraction. Mass signals of a signal / noise ratio of at least 2 were considered and only MS signals matching an O-glycan composition were considered for further analysis and annotated. Subsequent MS post-data acquisition analysis were made using mMass. RESULTS The results in TABLE 5 showed that the mAb PB223 selectively identifies O-glycans 03, 04, 030, 053 and 083 in the O-glycan array.TABLE 6 presents the O-glycan profiles of OV-90, HCC-1937 and LOVO detailing m / z, composition, proposed structures, and relative abundance of most expressed O-glycans. TABLE 6: O-glycan profile and relative abundance of HCC-1937, OV-90 and LOVO cell linesATTY. DOCKET NO.1143282.005213TABLE 6: O-glycan profile and relative abundance of HCC-1937, OV-90 and LOVO cell lines (Continued)ATTY. DOCKET NO.1143282.005213Analysis of O-glycan profile of OV-90 and HCC-1937 reveals identical monosaccharide compositions in the core 2 O-glycans 030 and 053, with 053 sharing the same composition as m / z 1040.4 (TABLE 6), and 030 coinciding with m / z 878.3 (TABLE 6). Conversely, LOVO exhibits a significantly lower percentage of 053 expression (0.29%) compared to OV-90 (6.76%) and HCC-1937 (6.32%) as m / z 1040.4. Notably, PB223 demonstrates reactivity towards OV-90 and HCC-1937 but not LOVO, consistent with the core 2 O-glycan 053 serving as the binding epitope of PB223. TABLE 7. HL60, U937 and K562 O-glycan profileATTY. DOCKET NO.1143282.005213To reinforce this finding, as is shown in TABLE 7, we also examined O-Glycan profile of the K562 cell line (chronic myeloid leukemia). This cell line exclusively expresses the 053 core 2 O-glycan as m / z 1821.9. (See TABLE 7). It is noted that the K562 cell line demonstrates strong reactivity to PB223 (84.6% of cells reactive with PB223) (See FIG.17). Immunohistochemistry (IHC) Analysis Showing Binding of PB223 to Different Human Tumor Tissues MATERIALS AND METHODSATTY. DOCKET NO.1143282.005213 Immunohistochemistry analysis was performed using PB223. OV-90 cells fixed in buffer for formalin fixed paraffin embedded (FFPE) embedding and sectioning served as positive control. FFPE samples of triple negative breast cancer (TNBC) were derived from TNBC tissue blocks. Additionally, PPFE samples from human tissue microarray (MC2082D, Tissue Array Com. LLC, Derwood, MD)( https: / / www.tissuearray.com / tissue- arrays / Multiple_Organ_Tumor / MC2082D). were utilized. This tumor microarray (TMA) encompassed a diverse array of tumor types across multiple organs. Specifically, it included 8 cases of adenosarcomas of the stomach, 4 cases each of adenocarcinoma and squamous cell carcinoma of the esophagus, 8 cases of adenocarcinoma of the colon, 8 cases of hepatocellular carcinoma of the liver, 8 cases of adenocarcinoma of the pancreas, 2 cases each of squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and small cell carcinoma of the lung. Additionally, there were 4 cases each of brain astrocytoma and glioblastoma, 8 cases of lymphoma of the spleen, 4 cases each of thyroid papillary carcinoma and follicular carcinoma.4 cases each of lymph node Hodgkin’s lymphoma and non-Hodgkin’s lymphoma, 16 cases of squamous cell carcinomas of the head and neck and skin, 4 cases each of fibrosarcoma and liposarcoma, 8 cases of malignant melanoma, 8 cases each of invasive ductal carcinoma and invasive lobular carcinoma of the breast. 16 cases of ovary tumor, 8 cases of endometrioid adenocarcinoma, 8 cases of squamous cell carcinoma of the cervix, 8 cases of adenocarcinoma of the prostate, 8 cases of seminoma of the testis, 8 cases of clear cell carcinoma of the kidney, and 8 cases of urothelial carcinoma of the bladder, single core per case. Experiments were performed to refine the concentration of PB223 for IHC analysis. Three concentrations (10, 2 and 0.4 µg / mL) were evaluated. PB223 was diluted with ER2 for 20 minutes. The optimal concentration determined was 10 µg / mL, with an incubation time of one hour. Abcam, anti-human IgG antibody, sku#ab2410 was used in this assay. IHC detection was carried out using the Bond Polymer Refine Detection System. Bond Polymer Refine Detection contains a peroxide block, post primary, polymer reagent, DAB chromogen and hematoxylin counterstain. RESULTSATTY. DOCKET NO.1143282.005213 These immunohistochemistry (IHC) experiments demonstrated PB223’s reactivity with various types of tumor tissues. For the TMA IHC analysis the following tumor tissue cores reacted with PB223: a. 6 / 8 stomach cancers. b. 3 / 8 Esophagus cancers. c. 7 / 8 colon carcinomas. d. 4 / 8 hepatocellular carcinoma. e. 7 / 8 pancreatic cancer. f. 2 / 2 lung papillary adenocarcinoma. g. 1 / 2 large lung carcinoma h. 1 / 8 spleen (diffuse B-cell lymphoma) i. 3 / 8 thyroid gland adenocarcinoma. j. 6 / 8 uterus (endometrioid adenocarcinoma). k. 2 / 8 cervical carcinoma. l. 11 / 16 ovarian carcinoma. m. 6 / 16 Breast carcinoma. n. 4 / 9 head and neck carcinoma. o. 8 / 22 skin cancers p. 3 / 8 prostate cancer q. 2 / 8 testis cancer r. 6 / 8 kidney cancer s 1 / 8 bladder cancer Some human tumor types not present in the TMA, were prepared by the inventors. Particularly, 2 distinct triple negative breast cancer samples were prepared by the inventors.ATTY. DOCKET NO.1143282.005213 The IHC results showed thar both triple negative breast cancer samples were reactive with PB223. The results of these IHC experiments are in the figures. FIG. 18 through FIG. 37 contain positive IHC images (DAB chromogen staining as seen by brown color), while FIG.38 and FIG.39 contain negative IHC images (absence of DAB chromogen staining as reflected by the absence of brown color). The IHC images contained in these IHC images respectively show that PB223 binds to stomach cancer cells (FIG. 18), esophageal cancer cells (FIG.19), colon cancer cells (FIG.20, 21), hepatocellular carcinoma cells (FIG.22), pancreatic cancer cells (FIG. 23), lung papillary adenocarcinoma cells (FIG. 24), thyroid cancer cells (FIG. 25), head and neck cancer cells (FIG. 26), breast cancer cells (FIG. 27), ovarian cancer cells (FIG. 28), endometrioid adenocarcinoma cells (FIG.29), cervical cancer cells (FIG.30), prostate cancer cells (FIG. 31), testicular cancer cells (FIG. 32), kidney cancer cells (FIG. 33), bladder cancer cells (FIG. 34), OV-90 cells (FIG. 35), and triple negative breast cancer (TNBC) cells (FIG. 36 and 37). The negative IHC images contained FIG.38 and FIG.39 (reflected by the absence of DAB chromogen staining, i.e., no brown color) respectively show that PB223 did not bind to a tested skin cancer cell line or to a thyroid cancer cell line. Immunohistochemistry (IHC) Analysis Of PB223 with Different Normal Human Tissues MATERIALS AND METHODS Immunochemistry analysis was performed using normal human tissues fixed in buffer for formalin-fixed, paraffin-embedded (FFPE) and sectioning. These normal tissues encompassed a diverse type of normal tissues across multiple organs. Specifically, the samples included 1 case of normal human brain, 3 cases each of normal human liver, lung, colon, and lymph node. Experiments were conducted similarly to the previously described method for tumor tissue array. In brief, PB223 was used at a concentration of 10 µg / mL for IHC analysis. The slides were deparaffinized and rehydrated through the following steps: two 15-minute immersion in xylene, followed by two 5-minute immersion in 100% alcohol, and a 5-minute immersion in 70% alcohol. Subsequently, the slides were washed after being removed fromATTY. DOCKET NO.1143282.005213 the 70% alcohol. They were then transferred to an antigen retrieval buffer (citric acid based; pH 6). After antigen retrieval the slides were brought to room temperature. The slides were washed three times for 5 minutes each in TBS, TBS, and TBST (Tris- buffer saline with Tween 20), respectively. A peroxidase blocking solution was the applied to the sections and incubated at room temperature for 10 minutes, followed by another wash as described before. The sections were blocked with 2.5% normal horse serum and incubated at room temperature for 30 minutes. After blocking, the sections were incubated overnight at 4oC with PB223 (10 µg / mL) or isotype control antibody (10 µg / mL) in normal horse serum. The following morning, the slides were washed again as previously described. The secondary antibody (horse anti-mouse HRP) was applied and incubated for one hour at room temperature. The slides were washed again, then DAB was applied to each section, and the stain was allowed to develop for 10 minutes. Finally, the sections were counter stained with hematoxylin. Detection was carried out using a Pannoramic 1000 Scanner for bright-field scanning. RESULTS The results of these immunohistochemistry (IHC) experiments demonstrated PB223 did not bind to any of the normal human tissues which were tested (1 case of normal human brain, 3 cases each of normal human liver, lung, colon, and lymph node) as compared to isotype control. In contrast, as we previously described, PB223 exhibited positive binding various types of tumor tissues. FIG.40 through FIG.49 contain representative negative IHC images showing that PB223 does not bind to these normal tissues as reflected by the absence of DAB chromogen staining (no brown color present). The IHC images in these Figures respectively showed that PB223 did not bind to normal brain tissue (FIG.40), the isotype control did not bind to brain tissue (FIG. 41), PB223 did not bind to normal liver tissue (FIG. 42), the isotype control antibody did not bind to normal liver tissue (FIG.43), PB223 did not bind to normal lung tissue (FIG.44), the isotype control antibody did not bind to normal lung tissue (FIG.45), PB223 did not bind to normal colon tissue (FIG.46), the isotype control antibody did not bind to normal colon tissue (FIG. 47), PB223 did not bind to normal lymph nodes (FIG. 48), and that the isotype control antibody did not bind to normal lymph nodes (FIG.49).ATTY. DOCKET NO.1143282.005213 EXAMPLE 11: IHC Analysis Showing Absence Of Binding of NEO-102 to Various Human Tumor Tissues (Which Are Bound by PB223) MATERIALS AND METHODS

[0426] Immunochemistry analysis was performed using human tumor tissues fixed in buffer for formalin-fixed, paraffin-embedded (FFPE) and sectioning. These tumor issues encompassed various types of human tumor tissues, including: ^ 3 cases of colon cancer ^ 6 cases of cervical cancer ^ 3 cases of prostate cancer ^ 3 cases of bladder cancer ^ 3 cases of head and neck squamous carcinoma ^ 6 cases of triple negative breast cancer ^ 2 cases of kidney cancer ^ 2 cases of liver cancer IHC PROCEDURE: Experiments were conducted similarly to the previously described method for tumor tissue array. In brief, NEO-102 was used at a concentration of 10 µg / mL for IHC analysis. The slides were deparaffinized and rehydrated through the following steps: two 15-minute immersion in xylene, followed by two 5-minute immersion in 100% alcohol, and a 5-minute immersion in 70% alcohol. Subsequently, the slides were washed after being removed from the 70% alcohol. They were then transferred to an antigen retrieval buffer (citric acid based; pH 6). After antigen retrieval the slides were brought to room temperature. Blocking and incubation: The slides were washed three times for 5 minutes each in TBS, TBS, and TBST (Tris- buffer saline with Tween 20), respectively. A peroxidase blocking solution was the applied to the sections and incubated at room temperature for 10 minutes, followed by another wash as described before. The sections were blocked with 2.5% normal horse serum and incubated at room temperature for 30 minutes. After blocking, the sections were incubated overnight at 4o C with NEO-102 (10 µg / mL) in normal horse serum. Detection:ATTY. DOCKET NO.1143282.005213 The following morning, the slides were washed again as previously described. The secondary antibody (horse anti-mouse HRP) was applied and incubated for one hour at room temperature. The slides were washed again, then DAB was applied to each section, and the stain was allowed to develop for 10 minutes. Finally, the sections were counter stained with hematoxylin. Detection was carried out using a Panoramic 1000 Scanner for bright-field scanning. RESULTS Our immunohistochemistry (IHC) experiments demonstrated NEO-102 reacted with: ^ 2 of 3 colon cancer samples ^ 1 of 6 cervical cancer samples In contrast to PB223, NEO-102 did not bind to various types of solid tumors in these studies. ^ 3 cases of prostate cancer ^ 3 cases of bladder cancer ^ 3 cases of head and neck squamous carcinoma ^ 6 cases of triple negative breast cancer ^ 2 cases of kidney cancer ^ 2 cases of liver cancer This lack of binding was compared to the isotype control. FIG. 50 through FIG. 65 contain exemplary IHC images showing the absence of NEO-102 binding to specific human tumor tissues as indicated by the absence of DAB chromogen staining (no brown color present) and the absence of binding to the same specific human tumor tissues by the isotype control antibody. The experiments in these Figures are described as follows: FIG. 50 contains an IHC image showing the staining of a human colon cancer sample with the isotype control antibody. FIG.51 contains an IHC image showing the staining of a human colon cancer sample with NEO-102. FIG. 52 contains an IHC image showing the staining of a human cervical cancer sample with the isotype control antibody. FIG.53 contains an IHC image showing the staining of a human cervical cancer sample with NEO-102.ATTY. DOCKET NO.1143282.005213 FIG. 54 contains an IHC image showing the staining of a human prostate cancer sample with the isotype control antibody. FIG.55 contains an IHC image showing the staining of a human prostate cancer sample with NEO-102. FIG.56 contains an IHC image showing the staining of a human head & neck cancer sample with the isotype control antibody. FIG.57 contains an IHC image showing the staining of a human head & neck cancer sample with NEO-102. FIG. 58 contains an IHC image showing the staining of a human triple negative breast cancer sample with the isotype control antibody. FIG. 59 contains an IHC image showing the staining of a human triple negative breast cancer sample with NEO-102. FIG. 60 contains an IHC image showing the staining of a human bladder cancer sample with the isotype control antibody. FIG.61 contains an IHC image showing the staining of a human bladder cancer sample with NEO-102. FIG. 62 contains an IHC image showing the staining of a human kidney cancer sample with the isotype control antibody. FIG.63 contains an IHC image showing the staining of a human kidney cancer sample with NEO-102. FIG.64 contains an IHC image showing the staining of a human liver cancer sample with the isotype control antibody. FIG. 65 contains an IHC image showing the staining of a human liver cancer sample with NEO-102. Each document cited herein, including all patent and non-patent literature, published or unpublished patent applications, abstracts, and any other document cited, is hereby incorporated by reference in its entirety. Having fully described the invention, the following claims are now provided below.

Claims

ATTY. DOCKET NO.1143282.005213 What is claimed is:

1. An antibody or antibody fragment which is an affinity variant of NEO-102 (wherein NEO-102 comprises variable light (VL) and variable (VH) chain polypeptides comprising the amino acid sequences in Table 2), which affinity variant binds to the same MUC5AC variant antigen (comprising core 2 O-glycans) bound by NEO-102, and comprises a KD which is at least 2-fold, 3-fold or 4-fold less than that of NEO-102 (increase in the affinity binding is at least 2-fold, 3-fold or 4-fold higher).

2. The antibody or antibody fragment of claim 1, which comprises a variable heavy (VH) region and a variable light (VL) region comprising one or more of the following mutations relative to NEO-102: (i) (S→E) modificaƟon of VH residue 28, (ii) (N→I) modification at VH (CDR1) residue 35; (iii) (G→K) modificaƟon at VH (CDR2) residue 62; (v) (S→V) modificaƟon at VH (CDR2) residue 58; (vi) (A→G) modificaƟon at VL (CDR2) position 54; and a variable heavy (VH) region comprising (S→L) modificaƟon at VH (CDR2) residue 61.

3. The antibody or antibody fragment of claim 2, which comprises at least 2, 3, 4 or 5 of said modifications.

4. The antibody or antibody fragment of claim 1, 2 or 3, which comprises a variable heavy (VH) region and a variable light (VL) region comprising all the following mutations relative to NEO-102: (i) (S→E) modificaƟon at VH residue 28, (ii) (N→I) modification at VH (CDR1) residue 35; and (iii) (G→K) modificaƟon at VH (CDR2) residue 62.

5. The antibody or antibody fragment of claim 1, 2 or 3, which comprises a variable heavy (VH) region and a variable light (VL) region comprising all the following mutations relative to NEO-102: (i) (S→E) modificaƟon of VH residue 28, (ii) (N→I) modification at VH (CDR1) residue 35; (iii) (G→K) modificaƟon at VH (CDR2) residue 62; (iv) (S→V) modificaƟon at VH (CDR2) residue 58; and (v) (A→G) modificaƟon at VL (CDR2) position 54.

6. The antibody or antibody fragment of claim 1, 2 or 3, which comprises a variable heavy (VH) region and a variable light (VL) region comprising all the following mutations relative to NEO-102: (i) (S→E) modificaƟon at VH residue 28, (ii) (N→I) modification at VH (CDR1) residue 35; (iii) (G→K) modificaƟon at VH (CDR2) residue 62; and (S→L) modificaƟon at VH (CDR2) residue 61.ATTY. DOCKET NO.1143282.005213 7. An antibody or antibody fragment which comprises the identical CDRs as AHF-18095 (NEO-102m or PB223), or AHF-18104 or AHF-18100.

8. An antibody or antibody fragment according to any of the previous claims, comprising (i) a VH polypeptide possessing an amino acid sequence which possesses at least 90% sequence identity to the VH polypeptide of NEO-102, and (ii) a VL polypeptide possessing an amino acid sequence which possesses at least 90% sequence identity to the VL polypeptide of NEO-102.

9. An antibody or antibody fragment according to any of the previous claims, comprising (i) a VH polypeptide possessing an amino acid sequence which possesses at least 95% sequence identity to the VH polypeptide of NEO-102, and (ii) a VL polypeptide possessing an amino acid sequence which possesses at least 95% sequence identity to the VL polypeptide of NEO-102.

10. An antibody or antibody fragment according to any of the previous claims, comprising (i) a VH polypeptide possessing an amino acid sequence which possesses at least 98-99% sequence identity to the VH polypeptide of NEO-102 (excluding the CDR modifications), and (ii) a VL polypeptide possessing an amino acid sequence which possesses at least 98-99% sequence identity to the VL polypeptide of NEO- 102.

11. An antibody or antibody fragment according to any of the previous claims, comprising (i) a VH polypeptide possessing an amino acid sequence which is identical to the VH polypeptide of PB223, and (ii) a VL polypeptide which is identical to the VL polypeptide of PB223.

12. An antibody or antibody fragment according to any of the previous claims, comprising (i) a VH polypeptide possessing an amino acid sequence which is identical to the VH polypeptide of AHF-18104, and (ii) a VL polypeptide which is identical to the VL polypeptide of AHF-18104.

13. An antibody or antibody fragment according to any of the previous claims, comprising (i) a VH polypeptide possessing an amino acid sequence which is identical to the VH polypeptide of AHF-18100, and (ii) a VL polypeptide which is identical to the VL polypeptide of AHF-18100.

14. An antibody or antibody fragment according to any of the previous claims, which comprises an Fc or constant region, optionally a human Fc or constant region.ATTY. DOCKET NO.1143282.005213 15. An antibody or antibody fragment according to any of the previous claims, which comprises a human IgG1, IgG2, IgG3 or IgG4 Fc or constant region, which optionally comprises at least one modification that enhances or inhibits at least one antibody effector function.

16. An antibody or antibody fragment according to any of the previous claims, which is a Fab or scFv.

17. An antibody or antibody fragment according to any of the previous claims, which comprises a human IgG1, IgG2, IgG3 or IgG4 Fc or constant region, which comprises at least one modification that enhances or inhibits at least one antibody effector function selected from glycosylation, FcR binding, FcRN binding, phagocytosis, antibody dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC).

18. An immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) comprising an antibody or antibody fragment according to any of the previous claims.

19. An antibody or antibody fragment according to any of the previous claims, or immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR comprising same, which is expressed in a recombinant host cell, optionally a mammalian, yeast, fungal, plant, insect or bacterial cell.

20. An antibody or antibody fragment according to any of the previous claims, or immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR comprising same, which is expressed in a CHO, BHK, COS or Hela or HEK cell.

21. A nucleic acid or nucleic acids which encode for an antibody, antibody fragment, immunoconjugate, ADC, or CAR according to any of the previous claims.

22. An expression vector comprising the nucleic acid or nucleic acids of claim 21.

23. A recombinant cell which comprises an expression vector of claim 22.

24. The recombinant cell of claim 23, which is mammalian, yeast, fungal, plant, insect or bacterial cell.

25. The recombinant cell of claim 23, which is a CHO, BHK, COS or Hela or HEK (e.g., HEK-293) cell.

26. A diagnostic or therapeutic composition comprising an antibody or antibody fragment, immunoconjugate, antibody drug conjugate (ADC) or chimeric antigenATTY. DOCKET NO.1143282.005213 receptor (CAR) according to any one of the previous claims and a therapeutically or diagnostically acceptable carrier.

27. A therapeutic composition or therapeutic method comprising the administration of an antibody or antibody fragment, immunoconjugate, antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) according to any one of the previous claims and at least one other therapeutic agent.

28. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises an anti-cancer agent.

29. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises a checkpoint inhibitor antibody or checkpoint inhibitor fusion protein, a hormone, a cytokine, a growth factor, a chemotherapeutic, another anti-cancer antibody, or a combination of any of the foregoing.

30. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent targets the extrinsic apoptotic pathway.

31. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent targets the intrinsic apoptotic pathway.

32. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent targets the common apoptotic pathway.

33. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent enhances ADCC of cancer cells.

34. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises gemcitabine and / or cisplatin.

35. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises a death receptor (DR) agonist, optionally a DR ligand or fragment or variant thereof, further optionally TRAIL or a Fas ligand, TNF receptor 1 (TNFRI), TRAIL-R2, DR4, DR5, or CD95 (APO-1 / Fas).

36. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent activates said death receptor or sensitizes said death receptor to activation by another agent.

37. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises an extrinsic pathway agent that agonizes the extrinsic apoptotic pathway in cancer cells, optionally wherein said extrinsic pathway agentATTY. DOCKET NO.1143282.005213 targets PML-RARα, DR4 (TRAIL R1), and / or DR5 (TRAIL R2), further optionally wherein said extrinsic pathway agent comprises TRAIL polypeptide or an agonistic fragment thereof, a Dr4 agonist, a Dr5 agonist, or all trans retinoic acid (ATRA).

38. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises an Dr4 or Dr5 agonist, optionally an agonistic anti-Dr4 or anti-Dr5 monoclonal antibody, optionally selected from Apomab, HGS-ETR1, HGS- ETR2, and GS-TR2J.

39. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises necrosis factor alpha (TNF-alpha), tumor necrosis factor beta (TNF-beta, lymphotoxin alpha), lymphotoxin beta (LT-beta), TRAIL (Apo2L), CD95 (Fas, APO-I) ligand, TRAMP (DR3, Apo-3) ligand, DR4 ligand, DR6 ligand as well as fragments, variants, and derivatives thereof.

40. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises an anti-CD95 antibody, anti-TRAIL-R1 (DR4) antibody, anti-TRAIL-R2 (DR5) antibody, anti-DR6 antibody, anti TNF-R1 / 2 antibody and anti- TRAMP (DR3) antibody or a fragment or derivative thereof.

41. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises mapatumumab (HGS-ETR1), lexatumumab (HGS-ETR2), conatumumab (AMG655), dulanermin (AMG 951, APO2L / TRAIL, PRO1762, RG3639, rhApo2L / TRAIL), tigatuzumab (CS1008), TRAIL R (DR4-Specific Altrimer, Anaphore), HGS TR2J, LBY135, drozitumab (PR085780, apomab), SL231, SM164 with TRAIL R2, or TAS266.

42. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises a chemotherapeutic agent, optionally doxorubicin, etoposide, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, oxaliplatin, 2-deoxy-D- glucose, or a platin, or comprises a drug that targets a Fas pathway or a c-FLIP pathway.

43. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises 4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH), estradiol (E2), or delta-tocotrienol.

44. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises an intrinsic pathway agent that agonizes the intrinsicATTY. DOCKET NO.1143282.005213 apoptotic pathway in cancer cells, optionally wherein said intrinsic pathway agent comprises an agonist of a proapoptotic Bcl-2 family member, further optionally wherein said proapoptotic BCL-2 family member comprises Bax, Bak, Bad, Bcl-Xs, Bid, Bik, Bim, or Hrk or comprises an antagonist of an antiapoptotic Bcl-2 family member, optionally wherein said antiapoptotic Bcl-2 family member comprises Bcl-2, Bcl-XL, Bcl-W, Bfl-1, pr Mcl-1.

45. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises an agent that targets Bcl-1, BcI-XL, Bax, BCL-Xs and / or PML-RARα, optionally an agent that acts directly on the mitochondrial inner membrane, and agent that antagonizes the antiapoptotic members of the Bcl-2 protein family, or an agent that enhances the activity of the proapoptotic members of the Bcl-2 family of proteins such as Bax or comprises arsenic trioxide or lonidamine.

46. The therapeutic composition or therapeutic method of claim 27, wherein the other therapeutic agent comprises an antisense agent targeting Bcl-1, Bcl-XL, Bax, BCL-Xs, both Bcl-2 and Bcl-XL, clusterin, or comprises oblimersen sodium.

47. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent is an intrinsic pathway agent which comprises a small molecule, optionally a small molecule that recognizes the surface pocket of Bcl-2 or Bcl-XL or comprises Antimycin-A, HA14-1, synthetic BH3 organic peptides, or a derivative thereof. or comprises farnesyl-thiosalicylic acid (FTS), estradiol (E2),delta-tocotrienol, salinomycin, or curcumin.

48. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises an antimetabolite, alkylator, corticosteroid, radiation, monoclonal antibody, platin or PARP inhibitor.

49. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises epirubicin, cisplatin, dacarbazine, fludarabine / cyclophosphamide, dexamethasone, or doxorubicin.

50. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises FTS, CMH, TMS, estradiol (E2).

51. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises a cytostatic agent, cytocidal agent, actinomycin D,ATTY. DOCKET NO.1143282.005213 adriamycin, arsenic trioxide, asparaginase, bleomycin, busulfan, camptosar, carboplatinum, carmustine, chlorambucil, cisplatin, corticosteroids, colicheamicin, cyclophosphamide, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, fludarabine, fluorouracil, gemcitabine, gemcitabine, gemzar, hydroxyurea, idarubicin, ifosfamide, irinotecan, lomustine, melphalan, mercaptopurine, methotrexate, mitomycin, mitoxantrone, oxaliplatin, paclitaxel, platinol, platinex, procarbazine, raltitrexed, ricin, steroids, streptozocin, taxol, Taxotere, thioguanine, thiotepa, tomudex, topotecan, treosulfan, trihydrate, vinblastine, vincristine, vindesine, vinorelbine, vinorelbine, daunomycin, dactinomycin, esorubicin, mafosfamide, cytosine arabinoside, bis-chloroethylnitrosurea, mitomycin C, mithramycin, prednisone, hydroxyprogesterone, testosterone, tamoxifen, dacarbazine, hexamethylmelamine, pentamethylmelamine, amsacrine, chlorambucil, methylcyclohexylnitrosurea, nitrogen mustards, cyclophosphamide, 6- mercaptopurine, 6-thioguanine, cytarabine, 5-azacytidine, deoxyco-formycin, 4- hydroxyperoxycyclophosphoramide, 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (5- FUdR), colchicine, trimetrexate, teniposide, or diethylstilbestrol.

52. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises a DNA damaging agent, nucleophosmin, an agent which induces cellular damage as part of an enhanced or synergistic process with another agent, a catalytic antibody, prodrugs, CHK1 / 2 inhibitor, CBP-501, AZD7762, histone deacetylase inhibitor, vorinostat, tumour necrosis factor related apoptosis inducing ligand, BH3 mimetic, ABT737, small molecule inhibitors, tyrosine kinase inhibitors, imatinib mesylate, gefitinib, erlotinib, monoclonal antibodies, rituximab or trastuzumab.

53. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises a caspase activator, apoptin, or survivin.

54. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises an endocrine therapeutic, a biologic response modifier, interferon, interleukin, antibody, aptamer, siRNA, oligonucleotide, enzyme, ion channel and receptor inhibitor or activator, hyperthermia, cryotherapy, agent to attenuate any adverse effects, or antiemetic.ATTY. DOCKET NO.1143282.005213 55. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises an alkylating drug, mechlorethamine, chlorambucil, Cyclophosphamide, Melphalan, Ifosfamide, antimetabolite, Methotrexate, purine antagonist, pyrimidine antagonist, 6-Mercaptopurine, 5-Fluorouracil, Cytarabine, Gemcitabine, spindle poison, Vinblastine, Vincristine, Vinorelbine, Paclitaxel, podophyllotoxin, Etoposide, Irinotecan, Topotecan, antibiotic, doxorubicin, Bleomycin, Mitomycin, nitrosoureas, Carmustine, Lomustine, inorganic ion, Cisplatin, Carboplatin, enzyme, Asparaginase, hormone, Tamoxifen, Leuprolide, Flutamide, or Megestrol.

56. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises an agent that targets p53, p53 pathway members, IκB kinase, IKKβ, the proteasome / ubiquitin pathway, the 20S proteasome, the PI3K / Akt pathway, or mTOR.

57. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises ONY-015, INGN201, PS1145, Bortezomib, CCI779, RAD- 001, or an siRNA targeting MDM2.

58. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises mixed lineage kinase domain like (MLKL) protein, rapamycin (RAP) or derivatives and / or analogs thereof.

59. The therapeutic composition or therapeutic method of claim 27, wherein said other therapeutic agent comprises everolimus or RAD001; CCI-779, ABT578, SAR543, vancomycin (an ethyl analog of FK506), AP23573, AP23841, KU-0063794, INK-128, EX2044, EX3855, EX7518, compounds that bind to the ATP-binding cleft of mTOR, AZD08055, or OSIO27.

60. The therapeutic composition or therapeutic method of claim 27, wherein said affinity variant of NEO-102, optionally PB223 and said second therapeutic agent exhibit enhanced therapeutic efficacy relative to said affinity variant of NEO-102 and said second therapeutic agent administered individually.

61. The therapeutic composition or therapeutic method of claim 27, wherein said affinity variant of NEO-102, optionally PB223 and said second therapeutic agent exhibit therapeutic efficacy at a lower dosage than the effective dosage of saidATTY. DOCKET NO.1143282.005213 affinity variant of NEO-102 or said second therapeutic agent when administered individually.

62. The antibody or antibody fragment, immunoconjugate, ADC, or CAR, composition, or method according to any one of the foregoing claims, wherein the antibody is chimeric.

63. The antibody or antibody fragment, immunoconjugate, ADC, or CAR, composition, or method according to any one of the foregoing claims, wherein the antibody or antibody fragment is humanized.

64. A pharmaceutical composition comprising the antibody or antibody fragment, immunoconjugate, ADC, or CAR, according to any one of the foregoing claims, and a pharmaceutically acceptable carrier.

65. A kit comprising the antibody or antibody fragment, immunoconjugate, ADC, or CAR according to any one of the foregoing claims.

66. A method of treatment, comprising administering an antibody or antibody fragment, immunoconjugate, ADC, or CAR, or composition containing, or a cell expressing according to any of the foregoing claims to a subject in need thereof.

67. A method of treatment, comprising administering an antibody or antibody fragment, immunoconjugate, ADC, or CAR, or composition containing, or a cell expressing according to any of the foregoing claims to a subject in need thereof and further comprising administering radiation therapy to a subject.

68. The method of claim 67, wherein said radiation therapy comprises gamma-radiation, neutron beam radiotherapy, electron beam radiotherapy, proton therapy, brachytherapy, and systemic radioactive isotopes, which optionally provides for an enhanced or synergistic improvement in treatment efficacy relative to the additive effects of the antibody and radiation therapy alone.

69. The treatment method of any one of the previous claims, wherein said affinity variant of NEO-102 and said second therapeutic agent are administered to said subject together or separately and / or in combination.

70. The treatment method of any one of the previous claims, wherein said treatment results in apoptosis of cancer cells in said subject.

71. The treatment method of any one of the previous claims, wherein said cancer is selected from the group consisting of: a carcinoma, colon cancer, pancreatic cancer,ATTY. DOCKET NO.1143282.005213 lung cancer, prostate cancer, liver cancer, adenoma, melanoma, breast cancer, ovarian cancer, uterine cancer, cervical cancer, mesothelioma, and skin cancer.

72. A method of detecting a variant MUC5AC antigen (comprising core 2 O-glycans) or cancer cells which express said variant MUC5AC antigen (comprising core 2 O- glycans) using an antibody or antibody fragment according to any of the previous claims.

73. The method of claim 72 which is effected in vivo.

74. The method of claim 72 which is effected in vitro.

75. The detection method of any of the previous claims which is used to assess the disease status of a subject.

76. The detection method of any of the previous claims which is used to assess the treatment status of a subject, optionally after administration of an antibody or antibody fragment, immunoconjugate, ADC, or CAR, or composition according to any one of the foregoing claims or a cell which expresses antibody or antibody fragment, immunoconjugate, ADC, or CAR according to any one of the foregoing claims.

77. The detection method of any of the previous claims which includes any one of the following: Western blot, radioimmunoassay, ELISA (enzyme linked immunosorbent assay), "sandwich" immunoassay, immunoprecipitation assay, precipitation reaction, gel diffusion precipitation reaction, immunodiffusion assay, agglutination assay, complement-fixation assay, immunohistochemical assay, fluorescent immunoassay, and protein A immunoassay.

78. The treatment or detection method or composition of any one of the previous claims, which further includes one or more antibodies identified in TABLE 1.

79. A method of detecting a variant MUC5AC antigen (comprising core 2 O-glycans) or cancer cells which express said variant MUC5AC antigen (comprising core 2 O- glycans) using an antibody or antibody fragment according to any one of the previous claims.

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