CD 40 Binding Molecules and CTL Pepetides for Treating Tumors

Abstract

Disclosed is a method and composition for treating tumors or infectious diseases, wherein the composition includes CD40 binding molecules together with CTL-activating peptides, e.g., tumor antigens. Such composition is useful for enhancing the anti-tumor effect of a peptide tumor vaccine, or for otherwise activating CTLs so that the activated CTLs can act against tumorous or infected cells. The CD40 binding molecules can include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab′) 2 and Fv, as well as other molecules including peptides, oligonucleotides, peptidomimetics and organic compounds which bind to CD40 and activate the CTL response.

1 . A pharmaceutical composition comprising
 (a) an activating anti-CD40 antibody,   (b) a CTL-activating peptide, and   (c) a pharmaceutically acceptable excipient or diluent.   
     
     
         2 . The pharmaceutical composition of  claim 1  wherein the CTL-activating peptide is a tumor peptide or a viral peptide. 
     
     
         3 . The pharmaceutical composition of  claim 2  wherein the CTL-activating peptide is a tumor peptide. 
     
     
         4 . The pharmaceutical composition of  claim 2  wherein the CTL-activating peptide is a viral peptide. 
     
     
         5 . The pharmaceutical composition of  claim 1  wherein the CTL-activating peptide is an HPV16 CTL-activating peptide. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the activating anti-CD40 antibody has reduced immunogenicity to avoid an immune response against itself in a subject to which it is administered. 
     
     
         7 . The pharmaceutical composition of  claim 2 , wherein the activating anti-CD40 antibody has reduced immunogenicity to avoid an immune response against itself in a subject to which it is administered. 
     
     
         8 . The pharmaceutical composition of  claim 3 , wherein the activating anti-CD40 antibody has reduced immunogenicity to avoid an immune response against itself in a subject to which it is administered. 
     
     
         9 . The pharmaceutical composition of  claim 4 , wherein the activating anti-CD40 antibody has reduced immunogenicity to avoid an immune response against itself in a subject to which it is administered. 
     
     
         11 . The pharmaceutical composition of  claim 6  wherein the activating anti-CD40 antibody is human, humanized, chimeric or Deimmunised™. 
     
     
         12 . The pharmaceutical composition of  claim 7  wherein the activating anti-CD40 antibody is human, humanized, chimeric or Deimmunised™. 
     
     
         13 . The pharmaceutical composition of  claim 8  wherein the activating anti-CD40 antibody is human, humanized, chimeric or Deimmunised™. 
     
     
         14 . The pharmaceutical composition of  claim 9  wherein the activating anti-CD40 antibody is human, humanized, chimeric or Deimmunised™. 
     
     
         15 . A method of treating a tumor in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 8  in an amount effective to treat said tumor, wherein the tumor expresses an antigen (a) that comprises or corresponds to the tumor peptide, or (b)
 from which the tumor peptide was derived.   
     
     
         16 . The method of  claim 15  wherein the subject is a human and the activating anti-CD40 antibody is human, humanized, chimeric or Deimmunised™. 
     
     
         17 . The method of  claim 15  wherein the pharmaceutical composition is administered directly into the tumor. 
     
     
         18 . A method of treating a viral infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 9  in an amount effective to treat said infection, wherein virus-infected cells
 in the subject express an antigen (a) that comprises or corresponds to the viral peptide, or (b) from which the viral peptide was derived   
     
     
         19 . The method of  claim 18  wherein the subject is a human and the activating anti-CD40 antibody is human, humanized, chimeric or Deimmunised™.