Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics

Abstract

This invention relates to a novel target for production of immune and non-immune based therapeutics and for disease diagnosis. More particularly, the invention provides therapeutic antibodies against VSIG1, ILDR1, LOC253012, AI216611, C1ORF32 or FXYD3 antigens, which are predicted co-stimulatory family members and which are differentially expressed in cancers including, lung cancer, ovarian cancer, and colon cancer, and diagnostic and therapeutic usages. The use of these antibodies for modulating B7 costimulation and related therapies such as the treatment of autoimmunity are also provided. This invention further relates to the discovery of extracellular domains of VSIG1 and its variants, FXYD3 and its variants, ILDR1 and its variants, LOC253012 and its variants, AI216611 and its variants, and C1ORF32 and its variants awhich are suitable targets for immunotherapy, cancer therapy, and drug development.

1 - 221 . (canceled) 
     
     
         222 . A method of treating cancer in a subject in need thereof, comprising administering to the subject a monoclonal or polyclonal antibody, or an antigen binding fragment thereof, comprising an antigen binding site that binds specifically to a polypeptide consisting of a sequence selected from the group consisting of SEQ ID NOs: 48, 50, 147, 148 and 299. 
     
     
         223 . The method of  claim 222 , wherein the cancer is selected from the group consisting of hematological malignancies, and soft tissue or solid tumors. 
     
     
         224 . The method of  claim 223 , wherein the hematological malignancies are selected from the group consisting of acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, multiple myeloma, Hodgkin's lymphoma and Non-Hodgkin's lymphoma. 
     
     
         225 . The method of  claim 223 , wherein the soft tissue or solid tumors are selected from the group consisting of cancer of breast, prostate, colon, ovary, spleen, kidney, bladder, head and neck, uterus, testicles, stomach, cervix, liver, bone, skin, pancreas and brain. 
     
     
         226 . The method of  claim 225  wherein the cancer is selected from the group consisting of lung cancer, ovarian cancer or colon cancer, and wherein the lung cancer, the ovarian cancer or the colon cancer is non-metastatic, invasive or metastatic. 
     
     
         227 . The method of  claim 223 , wherein the cancer is selected from the group consisting of non-metastatic, invasive and metastatic forms. 
     
     
         228 . The method of  claim 222 , wherein the antigen binding site contains at least 3-7 contiguous or non-contiguous amino acids. 
     
     
         229 . The method of  claim 228 , wherein the antigen binding site is a conformational or linear epitope containing 5-7 amino acids. 
     
     
         230 . The method of  claim 222 , wherein the antibody is a fully human antibody. 
     
     
         231 . The method of  claim 222 , wherein the antibody is a chimeric antibody. 
     
     
         232 . The method of  claim 222 , wherein the antibody is a humanized or primatized antibody. 
     
     
         233 . The method of  claim 222 , wherein the fragment is selected from the group consisting of Fab, Fab′, F(ab′)2, F(ab′), F(ab), Fv or scFv fragment and minimal recognition unit. 
     
     
         234 . The method of  claim 222 , wherein the antibody or fragment is coupled to a detectable marker, or to an effector moiety. 
     
     
         235 . The method of  claim 234 , wherein the effector moiety is an enzyme, a toxin, a therapeutic agent, or a chemotherapeutic agent. 
     
     
         236 . The method of  claim 235 , wherein the detectable marker is a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound or a chemiluminescent compound. 
     
     
         237 . The method of  claim 222 , further comprising administering an anticancer vaccine and potentiating a secondary immune response to a cancer antigen in a subject. 
     
     
         238 . The method of  claim 222 , wherein the cancer is a malignancy that expresses the protein of SEQ ID NO:50. 
     
     
         239 . The method of  claim 222 , further comprising co-administering a chemotherapeutic agent. 
     
     
         240 . The method of  claim 239 , wherein said chemotherapeutic agent is selected from the group consisting of taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, antimetabolites, alkylating agents, anthracyclines, antibiotics, anti-mitotic agents, duocarmycins, calicheamicins, maytansines and auristatins. 
     
     
         241 . The method of  claim 240 , wherein said chemotherapeutic agent is selected from the group consisting of daunorubicin, doxorubicin, methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine, vincristine, vinblastine, dactinomycin, bleomycin, mithramycin, anthramycin AMC, mechlorethamine, thioepa chlorambucil, melphalan, carmustine, BSNU, lomustine CCNU, cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, cis-dichlorodiamine platinum II, DDP and cisplatin. 
     
     
         242 . The method of  claim 222 , wherein the antibody is administered in a pharmaceutically acceptable diluent or carrier.