Identification, Optimization And Use Of Cryptic HLA-B7 Epitopes For Immunotherapy

Abstract

The invention provides methods for identifying a HLA-B*0702-restricted cryptic epitope in an antigen, as well as methods for increasing the immunogenicity of HLA-B*0702-restricted cryptic epitopes. The HLA-B*0702-restricted cryptic epitopes and their cognate immunogenic epitopes are useful for stimulating an immune reaction against the cryptic epitopes in a subject. Accordingly, the invention further provides pharmaceutical compositions comprising a HLA-B*0702-restricted cryptic epitope or a cognate immunogenic epitope thereof, and vaccination kits comprising such epitopes. The novel materials of the invention are particularly useful for efficiently treating patients having an HLA-B*0702 phenotype.

What is claimed: 
     
         1 . A cryptic HLA-B*0702-restricted epitope having the sequence GPKHSDCLA (SEQ ID NO: 4). 
     
     
         2 . An immunogenic HLA-B*0702-restricted epitope having the sequence APKHSDCLA (SED ID NO:8). 
     
     
         3 . A chimeric polypeptide, comprising the cryptic HLA-B*0702-restricted epitope of  claim 1  and one, two, or more HLA-B*0702-restricted cryptic epitopes selected from the group consisting of GPKHSDCLA (SEQ ID NO: 4), SPKANKEIL (SEQ ID NO: 3), APRSPLAPS (SEQ ID NO: 2), and DPRRLVQLL (SEQ ID NO: 1). 
     
     
         4 . A chimeric polypeptide, comprising the immunogenic HLA-B*0702-restricted epitope of  claim 2  and one, two, or more immunogenic HLA-B*0702-restricted epitopes selected from the group consisting of APKHSDCLA (SED ID NO:8), APKANKEIL (SED ID NO:7), APRSPLAPL (SED ID NO:6), and APRRLVQLL (SED ID NO:5). 
     
     
         5 . A pharmaceutical composition comprising at least, as an active principle, a HLA-B*0702-restricted cryptic epitope according to  claim 1 . 
     
     
         6 . A pharmaceutical composition comprising at least, as an active principle, an immunogenic HLA-B*0702-restricted epitope polypeptide according to  claim 2 . 
     
     
         7 . A pharmaceutical composition comprising at least, as an active principle, a chimeric polypeptide according to  claim 3 . 
     
     
         8 . A pharmaceutical composition comprising at least, as an active principle, a chimeric polypeptide according to  claim 4 . 
     
     
         9 . The pharmaceutical composition of  claim 5 , which is a vaccine. 
     
     
         10 . A kit of parts comprising, in separate formulations, a first peptide having the sequence of a HLA-B*0702-restricted cryptic epitope according to  claim 1 , and a second peptide having an HLA-B*0702-restricted immunogenic epitope cognate to the HLA-B*0702-restricted cryptic epitope of the first peptide. 
     
     
         11 . A kit of parts comprising, in separate formulations, a first chimeric polypeptide according to  claim 3 , and a second chimeric polypeptide comprising HLA-B*0702-restricted immunogenic epitopes cognate to the HLA-B*0702-restricted cryptic epitopes comprised in the first chimeric polypeptide. 
     
     
         12 . The kit according to  claim 10 , which is a vaccination kit, wherein said first and second peptides or chimeric polypeptides are in separate vaccination doses. 
     
     
         13 . The vaccination kit according to  claim 12 , which comprises 2 or 3 doses of second peptide or chimeric polypeptide, and 3, 4, 5, 6 or up to 50 doses of first peptide. 
     
     
         14 . The vaccination kit according to  claim 12 , wherein each dose comprises 1 to 5 mg of peptide. 
     
     
         15 . The vaccination kit according to  claim 12 , wherein the vaccination doses are formulated for subcutaneous injection. 
     
     
         16 . The kit according to  claim 11 , which is a vaccination kit, wherein said first and second chimeric polypeptides are in separate vaccination doses. 
     
     
         17 . The vaccination kit according to  claim 16 , which comprises 2 or 3 doses of second chimeric polypeptide, and 3, 4, 5, 6 or up to 50 doses of first chimeric polypeptide. 
     
     
         18 . The vaccination kit according to  claim 16 , wherein each dose comprises 1 to 20 mg of chimeric polypeptide. 
     
     
         19 . The vaccine according to  claim 16 , wherein the vaccination doses are formulated for subcutaneous injection. 
     
     
         20 . An isolated nucleic acid molecule designed to cause the expression of a cryptic HLA-B*0702-restricted epitope according to  claim 1 .