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 reducing the tumor burden in a human subject in need thereof, comprising administering to a human subject therapeutically effective amount of a monoclonal antibody, or antigen-binding fragment thereof, that specifically binds to monoisalo-GM2 but does not bind to asialo-GM2, disialo-GM2, monosialo-GM3, disialo-GD1a, disialo-GD1b, asialo-GM1, monosialo-GM1, lysosialo-GM1, trisialo-GT1b, and disialo-GD3, such that tumor burden is reduced in the human subject in need thereof.  
     
     
         47 . The method of  claim 46 , wherein the monoclonal antibody, or antigen-binding fragment thereof, specifically binds to a living cancer cell.  
     
     
         48 . The method of  claim 47 , wherein the cancer cell is selected from a 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 47 , wherein the cancer cell is selected from a 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 47 , wherein the cancer cell is selected from a group consisting of a myeloma, a prostate cancer, a small cell lung cancer, a breast cancer, a pancreatic cancer, an ovarian cancer.  
     
     
         51 . The method of  claim 47 , wherein the antibody, or antigen-binding fragment thereof, inhibits proliferation of the cancer cell upon binding to the cell.  
     
     
         52 . The method of  claim 47 , wherein the antibody, or antigen-binding fragment thereof, induces apoptosis in the cancer cell upon binding to the cell.  
     
     
         53 . The method of  claim 47 , wherein the antibody, or antigen-binding fragment thereof, stimulates antibody-dependent cell-mediated cytotoxicity in the subject upon binding to the cell.  
     
     
         54 . The method of  claim 53 , wherein the antibody, or antigen-binding fragment thereof, induces death of the cancer cell.  
     
     
         55 . The method of  claim 51 , wherein the cancer cell is selected from the group consisting of a myeloma cancer cell, a melanoma cancer cell, and a small cell lung cancer cell.  
     
     
         56 . The method of  claim 51 , wherein the cancer cell is a T-cell lymphoma cancer cell.  
     
     
         57 . The method of  claim 52 , wherein the cancer 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.  
     
     
         58 . The method of  claim 52 , wherein the cancer cell is a melanoma cell.  
     
     
         59 . The method of  claim 46 , wherein the monoclonal antibody, or antigen-binding fragment thereof, binds to the same epitope of monosialo-GM2 as does the monoclonal antibody DMF10.167.4 produced by a hybridoma cell line deposited under ATCC No. PTA-405.  
     
     
         60 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, is chimeric, humanized, primatized, veneered, or fully human.  
     
     
         61 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, comprises an antibody heavy chain comprising the amino acid sequence of SEQ ID NO:22.  
     
     
         62 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, comprises a purified antibody heavy chain comprising a modification to an amino acid shown in SEQ ID NO:22, 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 with lysine.  
     
     
         63 . The method of  claim 46 , wherein the antibody, or antigen-binding fragment thereof, comprises a purified antibody, or antigen-binding fragment thereof, wherein the antibody, or antigen-binding fragment thereof, comprises at least one complementary determinant region (CDRs) amino acid sequence selected from the amino acid sequences shown in the group consisting 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.  
     
     
         64 . 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.  
     
     
         65 . A method for inhibiting proliferation of a myeloma tumor cell expressing a ganglioside antigen, the method comprising contacting a myeloma tumor cell expressing a ganglioside antigen with an effective amount of an antibody, wherein the antibody is an IgG that specifically binds to the ganglioside, such that proliferation of the myeloma tumor cell expressing the ganglioside is inhibited.  
     
     
         66 . A method for causing cell death of a myeloma tumor cell expressing a ganglioside antigen, the method comprising contacting a myeloma tumor cell expressing a ganglioside antigen with an effective amount of an antibody, wherein the antibody is an IgG that specifically binds to the ganglioside, such that the myeloma tumor cell expressing the ganglioside dies.  
     
     
         67 . A method for causing cell death of a melanoma tumor cell expressing a ganglioside antigen, the method comprising contacting a melanoma tumor cell expressing a ganglioside antigen with an effective amount of an antibody, wherein the antibody is an IgG that specifically binds to the ganglioside, such that the melanoma tumor cell expressing the ganglioside dies.  
     
     
         68 . A method for causing cell death of a small cell lung cancer (SCLC) tumor cell expressing a ganglioside antigen, the method comprising contacting a SCLC tumor cell expressing a ganglioside antigen with an effective amount of an antibody, wherein the antibody is an IgG that specifically binds to the ganglioside, such that the SCLC tumor cell expressing the ganglioside dies.  
     
     
         69 . A method for causing cell death of a lymphoma or leukemia tumor cell expressing a ganglioside antigen, the method comprising contacting a lymphoma or leukemia tumor cell expressing a ganglioside antigen with an effective amount of an antibody, wherein the antibody is an IgG that specifically binds to the ganglioside, such that the lymphoma or leukemia tumor cell expressing the ganglioside dies.  
     
     
         70 . A method for inhibiting proliferation of a lymphoma tumor cell expressing a ganglioside antigen, the method comprising contacting a lymphoma tumor cell expressing a ganglioside antigen with an effective amount of an antibody, wherein the antibody is an IgG that specifically binds to the ganglioside, such that proliferation of the lymphoma tumor cell expressing the ganglioside is inhibited.  
     
     
         71 . The method of  claim 65 , wherein the antigen is selected from the group consisting of monosialo-GM2, asialo-GM2, disialo-GM2, monosialo-GM3, disialo-GD1a, disialo-GD1b, asialo-GM1, monosialo-GM1, lysosialo-GM1, trisialo-GT1b, and disialo-GD3.  
     
     
         72 . The method of  claim 65 , wherein the antibody specifically binds the monosialo-GM2 antigen.  
     
     
         73 . The method of  claim 65 , wherein the antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, a human antibody, a veneered antibody, and a primatized antibody.  
     
     
         74 . The method of  claim 66 , wherein the tumor cell undergoes apoptotic cell death.