Antibodies to treat cancer

Abstract

Compositions and methods for the treatment of cancer, particularly melanoma, myeloma, small cell lung cancer, thymic lymphoma, T-cell lymphoma, B-cell lymphoma, osteosarcoma, and acute T-cell leukemia, are disclosed. Illustrative compositions include one or more anti-ganglioside antibodies and polynucleotides that encode such anti-ganglioside antibodies. These antibodies may be for example, hamster antibodies, chimeric human/hamster antibodies, or humanized antibodies. The disclosed compositions are useful, for example, in the treatment of cancer and can be used to induce apoptosis in a cancer cell.

1 .- 45 . (canceled) 
     
     
         46 . A method for inducing apoptosis in a tumor cell expressing monosialo GM2 comprising contacting the cell with a purified antibody, or antigen-binding fragment thereof, that specifically binds to monosialo-GM2 but does not bind asialo-GM2, disialo-GM2, monosialo-GM3, disialo-GD1a, disialo-GD1b, asialo-GM1, monosialo-GM1, lysosialo-GM1, trisialo-GT1b, and disialo-GD3, such that apoptosis is induced in the cell, and wherein the antibody or antigen-binding fragment thereof binds to the same epitope of monosialo-GM2 as does the monoclonal antibody DMF10.167.4, produced by the hybridoma cell line deposited under ATCC No. PTA-405. 
     
     
         47 . The method of  claim 46 , wherein the purified antibody, or antigen-binding fragment thereof, specifically binds the cell expressing monosialo GM2. 
     
     
         48 . The method of  claim 46 , wherein the cell is selected from the group consisting of a hematological malignancy tumor cell, a breast cancer tumor cell, an ovarian cancer tumor cell, a uterine cancer tumor cell, a lung cancer tumor cell, a gastrointestinal cancer tumor cell, a pancreatic cancer tumor cell, a liver cancer tumor cell, a biliary cancer tumor cell, a kidney cancer tumor cell, a skin cancer tumor cell, an adrenal cancer tumor cell, an endocrine cancer tumor cell, a brain cancer tumor cell, a neural cancer tumor cell, a bladder cancer tumor cell, a bone cancer tumor cell, a connective tissue cancer tumor cell, a squamous cell carcinoma tumor cell, an adenocarcinoma tumor cell and a mesothelioma cancer tumor cell. 
     
     
         49 . The method of  claim 46 , wherein the cell is selected from the group consisting of a melanoma, a T cell leukemia, an osteosarcoma, a T cell lymphoma, a renal cancer, a myeloma, a prostate cancer, a small cell lung cancer, a breast cancer, a pancreatic cancer, an ovarian cancer. 
     
     
         50 . The method of  claim 46 , wherein the cell is selected from the group consisting of a myeloma cell, a prostate cancer cell, a small cell lung cancer cell, a breast cancer cell, a pancreatic cancer cell, an ovarian cancer cell. 
     
     
         51 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, inhibits proliferation of the cancer cell upon binding to the cell. 
     
     
         52 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, stimulates antibody-dependent cell-mediated cytotoxicity in the subject upon binding to the cell. 
     
     
         53 . The method of  claim 46 , wherein the cell is selected from the group consisting of a myeloma cancer cell, a melanoma cancer cell, and a small cell lung cancer cell. 
     
     
         54 . The method of  claim 46 , wherein the cell is a T-cell lymphoma cell. 
     
     
         55 . The method of  claim 46 , wherein the cell is selected from the group consisting of a small cell lung cancer cell, a myeloma cancer cell, a melanoma cancer cell, and a leukemia cancer cell. 
     
     
         56 . The method of  claim 46 , wherein the cell is a melanoma cell. 
     
     
         57 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, is chimeric, humanized, primatized, veneered, or fully human. 
     
     
         58 . The method of  claim 46 , wherein the antibody comprises an antibody heavy chain comprising the amino acid sequence of SEQ ID NO:22. 
     
     
         59 . The method of  claim 46 , wherein the antibody comprises a purified antibody heavy chain comprising a modification to the amino acid sequence of the heavy chain variable region as defined in SEQ ID NO:22 or SEQ ID NO:24, the modification comprising the substitution of threonine at linear position 78 of the sequence of the heavy chain variable region of SEQ ID NO:22 or SEQ ID NO:24 with lysine. 
     
     
         60 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, comprises complementary determining region (CDR) of SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, and SEQ ID NO:18. 
     
     
         61 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, is conjugated to moiety selected from the group consisting of an anti-tumor agent, a chemotherapeutic drug, a toxin, an immunological response modulator, a cytokine, an enzyme, a radioisotope and a detectable label. 
     
     
         62 . The method of  claim 46 , wherein the antibody comprises a purified light chain sequence comprising the amino acid sequence of SEQ ID NO:21. 
     
     
         63 . The method of  claim 46 , wherein the cell is in vivo. 
     
     
         64 . The method of  claim 46 , wherein the cell is in vitro.