Novel antibody delivery system for biological response modifiers

Abstract

The present invention provides a novel conjugate comprising an antibody directed toward a cell surface associated antigen, wherein said antigen is selected from the group consisting of 15A8 antigen and ZME-018 antigen; and a biological response modifier moiety, wherein said moiety is selected from the group consisting of TNF-alpha, TNF-beta and Interleukin-1. In addition, the present invention also provides a method of treating proliferative cell diseases comprising administration of a cytocidally effective dose of the composition of claim 1 to an individual in need of said treatment.

1 - 4 . (canceled)  
     
     
         5 . A method of treating cancer in a human patient in need of such treatment comprising administering to such patient a cytocidally effective dose of a composition comprising a protein with an antigen recognition site directed toward a cell surface associated antigen conjugated or fused to a biological response modifier, wherein it has been determined that cells of the patient's cancer express an antigen recognized and bound by the protein.  
     
     
         6 . (canceled)  
     
     
         7 . The method of  claim 5 , wherein said cancer is selected from the group consisting of breast cancer, cervical carcinoma and melanoma.  
     
     
         8 . The method of  claim 7 , wherein the patient has been diagnosed as having a breast tumor bearing a 1  5 A 8  tumor associated antigen and the protein is a monoclonal antibody that recognizes and binds to the 15A8 tumor associated antigen.  
     
     
         9 . The method of  claim 7 , wherein the patient has been diagnosed with a cervical carcinoma bearing a 15A8 tumor associated antigen and the protein is a monoclonal antibody that recognizes and binds to the 158A tumor associated antigen.  
     
     
         10 . The method of  claim 7 , wherein the patient has been diagnosed with cancer and cells of the cancer express an antigen recognized by monoclonal antibody ZME-018, and further wherein the protein is a monoclonal antibody that recognizes and binds the antigen.  
     
     
         11 - 12 . (canceled)  
     
     
         13 . The method of  claim 5 , wherein the biological response modifier is a cytokine.  
     
     
         14 . The method of  claim 13 , wherein the cytokine is TNF.  
     
     
         15 . The method of  claim 14 , wherein the TNF is TNF-beta.  
     
     
         16 . The method of  claim 14 , wherein the TNF is TNF-alpha.  
     
     
         17 . The method of  claim 13 , wherein the cytokine is an interleukin.  
     
     
         18 . The method of  claim 17 , wherein the interleukin is interleukin-1 or interleukin-6.  
     
     
         19 . The method of  claim 13  wherein the cytokine is an interferon.  
     
     
         20 . The method of  claim 5 , wherein the protein's antigen recognition site recognizes and binds to the 15A8 tumor associated antigen.  
     
     
         21 . The method of  claim 5 , wherein the protein's antigen recognition site recognizes and binds to the ZME-018 antigen.  
     
     
         22 . The method of  claim 5 , wherein the protein's antigen recognition site recognizes and binds to the antigen recognized by the 465.12 antibody.  
     
     
         23 . The method of  claim 5 , wherein the protein with an antigen recognition site is fused to the biological response modifier.  
     
     
         24 . The method of  claim 5 , wherein the protein with an antigen recognition site is conjugated to the biological response modifier.  
     
     
         25 . The method of  claim 14 , wherein the protein's antigen recognition site recognizes and binds to the ZME-018 antigen.  
     
     
         26 . The method of  claim 5 , further defined as comprising the steps of: 
 (a) identifying a patient having a tumor, which tumor comprises cells for targeting and wherein those cells comprise a cell surface antigenic marker at concentrations in excess of that found at other non-target sites;    (b) obtaining a composition comprising a protein with an antigen recognition site directed toward a cell surface associated antigen conjugated or fused to the biological response modifier, wherein it has been determined that cells of the patient's cancer express an antigen recognized and bound by the protein with an antigen recognition site; and    (c) administering an amount of the composition to the patient effective to treat the cancer.    
     
     
         27 . The method of  claim 26 , wherein the patient is diagnosed as having a tumor with a specific antigenic determinant that will allow targeting and concentration of the biological response modifier at the site where it is needed to kill tumor cells.  
     
     
         28 . The method of  claim 5 , wherein the protein is an antibody.  
     
     
         29 . The method of  claim 28 , wherein the antibody is a monoclonal antibody.