Therapeutic binding agents against MUC-1 antigen and methods for their use

Abstract

The invention provides therapeutic compositions comprising binding agents that specifically bind to tumor-associated MUC-1 and reduce, reverse or prevent their effects in cancer. More particularly, the invention provides therapeutic compositions that comprise a binding agent that can specifically bind to an epitope that comprises both peptide and carbohydrate on such tumor-associated MUC-1. The invention further provides methods for the use of such therapeutic compositions in the treatment of cancer. The invention also provides methods for therapeutically treating a mammal bearing a tumor comprising administering to the mammal an effective amount of a therapeutic composition consisting essentially of a binding agent that specifically binds to an epitope of tumor-associated MUC1, wherein the mammal generates an immune response that comprises an antibody that specifically binds to an epitope of tumor-associated MUC1 that is different from the epitope of tumor associated MUC1 that is specifically bound by the binding agent.

1 - 15 . (canceled)  
     
     
         16 . A method for therapeutically treating a mammal bearing a tumor, the method comprising administering to the mammal an effective amount of a therapeutic composition consisting essentially of a non-radiolabeled binding agent that specifically binds to an epitope of tumor-associated MUC1, wherein the mammal generates an immune response that comprises an antibody that specifically binds to an epitope of tumor-associated MUC1 that is different from the epitope of tumor associated MUC1 that is specifically bound by the binding agent.  
     
     
         17 . (canceled)  
     
     
         18 . The method of  claim 16 , wherein the binding agent is not a monoclonal antibody selected from: HMPV, VU-3-C6, MF06, VU-11-D1, MF30, BCP8, DF3, BC2, B27.29, VU-3-D1, 7540MR, MF11, Bc4E549, VU-11-E2, M38, E29, GP1.4, 214D4, BC4W154, HMFG-2, C595, Mc5, and A76-A/C7.  
     
     
         19 . The method of  claim 16 , wherein the binding agent and the tumor-associated MUC1 form a complex.  
     
     
         20 . The method of  claim 19 , wherein the immune response is generated by the complex.  
     
     
         21 . The method of  claim 16 , wherein the immune response also includes a T cell response.  
     
     
         22 . The method of  claim 16 , wherein the binding agent is Alt-1.  
     
     
         23 . The method of  claim 16 , wherein the mammal is a human.  
     
     
         24 . The method of  claim 16 , wherein the epitope to which the binding agent specifically binds comprises an immunological determinant that includes carbohydrate.  
     
     
         25 . The method of  claim 16 , wherein the binding agent is administered intravenously.  
     
     
         26 . The method of  claim 16 , wherein the binding agent is administered subcutaneously.  
     
     
         27 . The method of  claim 16 , wherein the binding agent is administered at a dosage of less that 8 mg/30 kg body weight.  
     
     
         28 . The method of  claim 16 , wherein the binding agent is administered at a dosage of less than about 3 mg/30 kg of body weight.  
     
     
         29 . The method of  claim 16 , wherein the binding agent is administered at a dosage of about 2 mg/patient.  
     
     
         30 . A therapeutic composition consisting essentially of a non-radiolabeled binding agent that specifically binds to an epitope of tumor-associated MUC-1 and that is effective in therapeutically treating a mammal having a tumor that expresses a tumor-associated MUC-1.  
     
     
         31 . A therapeutic composition comprising a binding agent, other than HMFG1, that specifically binds to an epitope of tumor-associated MUC-1 and that is effective in therapeutically treating a mammal having a tumor that expresses a tumor-associated MUC-1.  
     
     
         32 . (canceled)  
     
     
         33 . The therapeutic composition according to  claim 30 , wherein the binding agent is not a monoclonal antibody selected from: HMPV, VU-3-C6, MF06, VU-11-D1, MF30, BCP8, DF3, BC2, B27.29, VU-3-D1, 7540MR, MF11, Bc4E549, VU-11-E2, M38, E29, GP1.4, 214D4, BC4W154, HMFG-2, C595, Mc5, and A76-A/C7.  
     
     
         34 . The therapeutic composition according to  claim 30 , wherein the binding agent binds immunological determinants from amino acid residues of a peptide having the amino acid sequence DTRPAP (SEQ ID NO: 5).  
     
     
         35 . A binding agent which binds the same epitope as Alt-1.  
     
     
         36 - 38 . (canceled)  
     
     
         39 . The therapeutic composition according to  claim 30 , wherein the binding agent is photoactivated.  
     
     
         40 . The therapeutic composition according to  claim 30 , wherein the binding agent is coupled to a photodynamic agent.  
     
     
         41 . The therapeutic composition according to  claim 40 , wherein photodynamic agents include hypocrellins and hypocrellin derivatives.