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.

1 - 20 . (canceled) 
     
     
         21 . An immunogenic HLA-B*0702-restricted epitope having the sequence APRRLVQLL (SEQ ID NO: 5). 
     
     
         22 . A chimeric polypeptide, comprising the peptide DPRRLVQLL (SEQ ID NO: 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). 
     
     
         23 . A chimeric polypeptide, comprising SEQ ID No: 5 and one, two or more immunogenic HLA-B*0702-restricted epitopes selected from the group consisting of APKHSDCLA (SEQ ID NO: 8), APKANKEIL (SEQ ID NO: 7), APRSPLAPL (SEQ ID NO: 6), and APRRLVQLL (SEQ ID NO: 5). 
     
     
         24 . A pharmaceutical composition comprising at least, as an active principle, an immunogenic HLA-B*0702-restricted epitope polypeptide according to  claim 21 . 
     
     
         25 . A pharmaceutical composition comprising at least, as an active principle, a chimeric polypeptide according to  claim 22 . 
     
     
         26 . A pharmaceutical composition comprising at least, as an active principle, a chimeric polypeptide according to  claim 23 . 
     
     
         27 . The pharmaceutical composition of any one of  claims 24  to  26 , which is a vaccine. 
     
     
         28 . A kit of parts comprising, in separate formulations, a first chimeric polypeptide according to  claim 22 , and a second chimeric polypeptide according to  claim 23 . 
     
     
         29 . The kit according to  claim 28 , which is a vaccination kit, wherein said first and second chimeric polypeptides are in separate vaccination doses. 
     
     
         30 . The vaccination kit according to  claim 29 , which comprises 2 or 3 doses of second chimeric polypeptide, and 3, 4, 5, 6 or up to 50 doses of first chimeric polypeptide. 
     
     
         31 . The vaccination kit according to  claim 29 , wherein each dose comprises 1 to 20 mg of chimeric polypeptide. 
     
     
         32 . The vaccination kit according to  claim 29 , wherein the vaccination doses are formulated for subcutaneous injection. 
     
     
         33 . A kit of parts comprising, in separate formulations, a chimeric polypeptide according to  claim 22  and an immunogenic peptide according to  claim 21 . 
     
     
         34 . The kit according to  claim 33 , which is a vaccination kit, wherein said chimeric polypeptide and immunogenic peptide are in separate vaccination doses. 
     
     
         35 . The vaccination kit according to  claim 33 , which comprises 2 or 3 doses of immunogenic peptide, and 3, 4, 5, 6 or up to 50 doses of chimeric polypeptide. 
     
     
         36 . The vaccination kit according to  claim 35 , wherein each dose comprises 1 to 20 mg of chimeric polypeptide or of immunogenic peptide. 
     
     
         37 . The vaccination kit according to  claim 33 , wherein the vaccination doses are formulated for subcutaneous injection.