Immunotherapeutic stress protein-peptide complexes against cancer

Abstract

Disclosed is a method for inhibiting the proliferation of a tumor in a mammal. The method involves the steps of (a) isolating a stress protein-peptide complex from tumor cells previously removed from the mammal and (b) administering the isolated stress protein-peptide complex back to the mammal in order to stimulate in the mammal an immune response against the tumor from which the complex was isolated. Stress protein-peptide complexes having particular utility in the practice of the instant invention include the Hsp70-peptide, Hsp90-peptide and gp96-peptide complexes.

What is claimed is:  
     
         1 . A method for inhibiting proliferation of a tumor in a mammal, the method comprising: 
 administering to the mammal harboring the tumor a composition comprising, 
 (a) an immunogenic stress protein-peptide complex isolated from a cell derived from the tumor, said complex being operative to initiate in the mammal an immune response against said tumor, and  
 (b) a pharmaceutically acceptable carrier,  
   in an amount sufficient to elicit in the mammal an immune response against the tumor thereby inhibiting proliferation of the tumor.    
     
     
         2 . The method of  claim 1 , wherein the stress protein in the complex is a Hsp70, a Hsp90 or a gp96.  
     
     
         3 . The method of  claim 1 , wherein a peptide in the complex is non covalently associated with the stress protein.  
     
     
         4 . The method of  claim 1 , wherein administering the complex initiates an immune response mediated by a T cell.  
     
     
         5 . The method of  claim 4 , wherein administering the complex initiates an immune response mediated by a cytotoxic T cell.  
     
     
         6 . The method of  claim 1 , wherein the complex is administered to the mammal in an amount in the range of about 1 to about 1000 micrograms of complex/kg body weight of mammal/administration.  
     
     
         7 . The method of  claim 6 , wherein said amount is in the range of about 100 to about 250 micrograms of complex/kg body weight of mammal/administration.  
     
     
         8 . The method of  claim 1 , wherein the complex is administered repeatedly to the mammal.  
     
     
         9 . The method of  claim 1 , wherein the composition is administered to the mammal in combination with a cytokine.  
     
     
         10 . A method for inhibiting proliferation of a tumor in a mammal, the method comprising the steps of: 
 (a) providing a tumor cell excised from the mammal,    (b) isolating from the cell an immunogenic stress protein-peptide complex operative to initiate in the mammal an immune response against the tumor cell, and    (c) administering to the mammal the isolated stress protein-peptide complex in an amount sufficient to elicit in the mammal an immune response against the tumor cell thereby to inhibit proliferation of any tumor cell remaining in the mammal.    
     
     
         11 . The method of  claim 10 , wherein the stress protein in the complex is a Hsp70, a Hsp90 or a gp96.  
     
     
         12 . The method of  claim 10 , wherein a peptide in the complex is non covalently associated with the stress protein.  
     
     
         13 . The method of  claim 10 , wherein administering the complex initiates an immune response mediated by a T cell.  
     
     
         14 . The method of  claim 13 , wherein administering the complex initiates an immune response mediated by a cytotoxic T cell.  
     
     
         15 . The method of  claim 10 , wherein the complex is administered to the mammal in an amount in the range of about 1 to about 1000 micrograms of complex/kg body weight of mammal/administration.  
     
     
         16 . The method of  claim 15 , wherein said amount is in the range of about 100 to about 250 micrograms of complex/kg body weight of mammal/administration.  
     
     
         17 . The method of  claim 10 , wherein the complex is administered repeatedly to the mammal.  
     
     
         18 . The method of  claim 10 , wherein said complex is administered to the mammal in combination with a cytokine.