IgE ANTIBODIES FOR THE TREATMENT OF CANCER

Abstract

The present invention provides monoclonal IgE antibodies comprising Fc epsilon (ε) constant regions and variable regions comprising at least one antigen binding region specific for binding a single epitope of a circulating, tumor-associated antigen (TAA) that is not a cell surface antigen wherein the epitope of the targeted antigen is not highly repetitive or is a non-repetitive epitope. The IgE antibodies of the invention are useful in the treatment of cancer associated with the tumor antigen. In one embodiment the TAA is prostate-specific antigen (PSA).

1 . An IgE monoclonal antibody that specifically binds a single epitope of a circulating, tumor-associated antigen that is not a cell surface antigen, wherein the epitope is not highly repetitive. 
     
     
         2 . The antibody of  claim 1  wherein the monoclonal antibody is a chimeric monoclonal antibody or a humanized monoclonal antibody. 
     
     
         3 . The antibody of  claim 1  having a constant region that is of human origin. 
     
     
         4 . The antibody of  claim 1  having variable regions that are of human origin, non-human origin or any combination thereof. 
     
     
         5 . The antibody of  claim 1  wherein the epitope is a non-repetitive epitope. 
     
     
         6 . The antibody of  claim 1  wherein said antibody is capable of eliciting an IgE-mediated immune response in a mammal. 
     
     
         7 . The antibody of  claim 1  wherein the circulating, secreted tumor-associated antigen is prostate-specific antigen (PSA). 
     
     
         8 . The antibody of  claim 7  which binds to the epitope of PSA defined by amino acids EEFLTPKKLQCVDLHVISNDVCAQV (SEQ ID NO: 1) of PSA. 
     
     
         9 . The antibody of  claim 7  which binds to the epitope of PSA defined by amino acids SIEPEEFLTPKKLQCVDLHVISNDVCAQV (SEQ ID NO: 3) of PSA or any portion thereof. 
     
     
         10 . The antibody of  claim 7  wherein the antibody is a chimeric monoclonal antibody, or a fully humanized monoclonal antibody. 
     
     
         11 . A method for inducing an IgE-mediated immune response against a circulating secreted tumor-associated antigen that is not a cell surface antigen in a subject capable of mounting said immune response comprising administering to the subject the antibody of  claim 1  in an amount effective to induce an IgE-mediated immune response in the mammal. 
     
     
         12 . The method of  claim 11  wherein the IgE-mediated immune response is induced in the mammal in the absence of systemic hypersensitivity reactions in the subject. 
     
     
         13 . The method of  claim 11  wherein the IgE-mediated immune response induced in the subject is capable of inhibiting the progression of a tumor secreting the antigen. 
     
     
         14 . The method of  claim 11  wherein the circulating, secreted, tumor associated antigen is PSA. 
     
     
         15 . The method of  claim 14  wherein the IgE-mediated immune response induced in the subject against PSA is capable of inhibiting tumor growth or causing tumor destruction of a tumor secreting PSA. 
     
     
         16 . A method of inducing a direct ADCC immune response, a direct ADCP immune response, or both, to a circulating TAA that is not a cell surface antigen in a subject capable of mounting such a response comprising administering to the subject an effective amount of an IgE monoclonal antibody that specifically binds a single epitope of the circulating antigen wherein the epitope is not highly repetitive or is non-repetitive, and wherein a direct IgE mediated ADCC or ADCP immune response against the antigen is elicited. 
     
     
         17 . The method of  claim 16  wherein the direct ADCC or ADCP immune response is elicited in the microenvironment of a tumor that is secreting the circulating TAA. 
     
     
         18 . The method of  claim 16  wherein the direct ADCC or ADCP immune response is induced in the absence of systemic hypersensitivity reactions in the subject. 
     
     
         19 . The antibody of  claim 7  which is genetically fused or chemically conjugated to a protein immunomodulator. 
     
     
         20 . A method of treating prostate cancer in a subject comprising administering to the subject a therapeutically effective amount of the IgE monoclonal antibody of  claim 7 .