Recombinant adenylate cyclase toxin of bordetella induces t cell responses against tumoral antigens

Abstract

An immunogenic composition comprising a recombinant protein comprising a Bordetella CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen is provided as a cancer treatment. Methods of treatment with this immunogenic composition are also provided. In an embodiment, the therapeutic composition is a treatment for melanoma, and comprises epitopes from the HLA*0201 epitope. These epitopes include Tyr or GnT-V, and are present in the recombinant proteins CyaA-E5-Tyr and CyaA-E5-GnT-V.

1 . An immunogenic composition comprising a recombinant protein, wherein the recombinant protein comprises a  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen. 
     
     
         2 . The immunogenic composition as claimed in  claim 1 , wherein the  Bordetella  CyaA, or fragment thereof, and the peptide are genetically fused or chemically bound together. 
     
     
         3 . The immunogenic composition as claimed in  claim 1 , wherein the  Bordetella  CyaA is detoxified. 
     
     
         4 . The immunogenic composition as claimed in  claim 1 , wherein the tumor is a melanoma. 
     
     
         5 . The immunogenic composition as claimed in  claim 1 , wherein the tumor antigen is an HLA*0201 epitope. 
     
     
         6 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is Tyr or GnT-V. 
     
     
         7 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is region 369-377 of tyrosinase. 
     
     
         8 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is from an intron of the N-acetylglucosominyl-transferase V gene. 
     
     
         9 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is YMDGTMSQV. 
     
     
         10 . The immunogenic composition as claimed in  claim 5 , wherein the HLA*0201 epitope is VLPDVFIRC. 
     
     
         11 - 22 . (canceled) 
     
     
         23 . A method of treating a patient with cancer comprising (1) administering a immunogenic composition to the patient, wherein the immunogenic composition comprises a recombinant protein, wherein the recombinant protein comprises a  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen, and (2) inducing a T cell response in the patient. 
     
     
         24 . The method as claimed in  claim 23 , wherein the T cell response is a CTL response. 
     
     
         25 . The method as claimed in  claim 23 , wherein the cancer is a melanoma. 
     
     
         26 . The method as claimed in  claim 23 , wherein the tumor antigen is an HLA*0201 epitope. 
     
     
         27 . The method as claimed in  claim 23 , wherein the HLA*0201 epitope is Tyr or GnT-V. 
     
     
         28 - 33 . (canceled) 
     
     
         34 . A method of treating a patient with cancer comprising (1) administering an immunogenic composition to the patient, wherein the immunogenic composition comprises a vector expressing a recombinant protein, wherein the recombinant protein comprises a  Bordetella  CyaA, or a fragment thereof, and a peptide that corresponds to a tumor antigen, and (2) inducing a T cell response in the patient. 
     
     
         35 . The method as claimed in  claim 34 , wherein the T cell response is a CTL response. 
     
     
         36 . The method as claimed in  claim 34 , wherein the cancer is a melanoma. 
     
     
         37 . The method as claimed in  claim 34 , wherein the tumor antigen is an HLA*0201 epitope. 
     
     
         38 . The method as claimed in  claim 34 , wherein the HLA*0201 epitope is Tyr or GnT-V. 
     
     
         39 - 44 . (canceled)