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 inhibiting tumor cell proliferation, comprising contacting a tumor cell with an effective amount of a monoclonal antibody, or antigen-binding fragment thereof, wherein the monoclonal antibody: 
 (a) binds to fetal thymocytes and inhibits proliferation of a cell upon binding to the cell but does not bind to adult thymocytes;    (b) binds to a cancer cell; and    (c) binds to a ganglioside,    such that tumor cell proliferation is inhibited.    
     
     
         47 . The method of  claim 46 , wherein the monoclonal antibody, or antigen-binding fragment thereof, induces homotypic aggregation upon binding to a cell.  
     
     
         48 . The method of  claim 46 , wherein the monoclonal antibody, or antigen-binding fragment thereof, induces apoptosis in a cell to which it binds upon binding to the cell.  
     
     
         49 . The method of  claim 46 , wherein the ganglioside is monosialo-GM2.  
     
     
         50 . The method of  claim 49 , wherein the monoclonal antibody, or antigen-binding fragment thereof, 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.  
     
     
         51 . The method of  claim 48 , wherein the monoclonal antibody, or antigen-binding fragment thereof, is an IgG.  
     
     
         52 . The method of  claim 46 , wherein the monoclonal antibody, or antigen-binding fragment thereof, is an antigen-binding fragment.  
     
     
         53 . The method of  claim 46 , wherein tumor cell proliferation is inhibited in a tumor cell in vitro.  
     
     
         54 . The method of  claim 46 , wherein tumor cell proliferation is inhibited in a tumor cell in vivo.  
     
     
         55 . A method for inhibiting tumor cell proliferation in a subject in need thereof, comprising administering to a subject a therapeutically effective amount of a monoclonal antibody, or antigen-binding fragment thereof, wherein the monoclonal antibody: 
 (a) binds to fetal thymocytes and inhibits proliferation of a cell upon binding to the cell but does not bind to adult thymocytes;    (b) binds to a cancer cell; and    (c) binds to a ganglioside;    such that tumor cell proliferation is inhibited in the subject.    
     
     
         56 . A method for inducing apoptosis in a cell in a subject in need thereof, comprising administering to a subject a therapeutically effective amount of a monoclonal antibody, or antigen-binding fragment thereof, wherein the monoclonal antibody: 
 (a) binds to fetal thymocytes and inhibits proliferation of a cell upon binding to the cell but does not bind to adult thymocytes;    (b) binds to a cancer cell; and    (c) binds to a ganglioside;    such that apoptosis is induced in a cell in the subject.    
     
     
         57 . A method for inducing apoptosis in a cell in vitro, comprising contacting a cell with an effective amount of a monoclonal antibody, or antigen-binding fragment thereof, wherein the monoclonal antibody: 
 (a) binds to fetal thymocytes and inhibits proliferation of a cell upon binding to the cell but does not bind to adult thymocytes;    (b) binds to a cancer cell; and    (c) binds to a ganglioside;    such that apoptosis is induced in the cell in vitro.    
     
     
         58 . A method for selectively delivering a moiety to a tumor cell in a mammal, the method comprising: 
 (a) administering to a mammal an effective amount of a monoclonal antibody, or antigen-binding fragment thereof, conjugated to a moiety selected from the group consisting of a radioactive molecule, a radionuclide, a sensitizer molecule, an imaging reagent, a radioisotope, a toxin, a cytotoxin, an anti-tumor agent, a chemotherapeutic agent, a modulator of the immune system, a cytokine, and a reporter group, wherein the monoclonal antibody: 
 (i) binds to fetal thymocytes and inhibits proliferation of a cell upon binding to the cell but does not bind to adult thymocytes;  
 (ii) binds to a cancer cell; and  
 (iii)binds to a ganglioside; and  
   (b) allowing sufficient time for the complex to bind to the tumor cell; such that the moiety is selectively delivered to the tumor cell in the mammal.