Identification, optimization and use of cryptic hla-b7 epitopes for immunotherapy
AssigneeVaxon Biotech
InventorsKostantinos (Kostas) Kosmatopoulos, Stéphanie Graff-Dubois, Jeanne Menez-Jamet
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Abstract
The present invention relates to the field of peptide immunotherapy. In particular, the invention pertains to a method for identifying a HLA-B*0702-restricted cryptic epitope in an antigen, and to a method for increasing its immunogenicity. The invention also provides novel methods and materials for efficiently treating patients having an HLA-B*0702 phenotype.
Claims35
A method for increasing the immunogenicity of a HLA-B*0702-restricted cryptic epitope, comprising a step of substituting the N-terminal residue of said epitope with an alanine, or substituting the C-terminal residue of said epitope with a leucine.
A method for increasing the immunogenicity of a HLA-B*0702-restricted cryptic epitope, wherein the three first residues of said cryptic epitope are APR or APK or APH or APM, comprising a step of substituting the C-terminal residue of said epitope with a leucine.
A method for increasing the immunogenicity of a HLA-B*0702-restricted cryptic epitope, wherein the second and the third residues of said cryptic epitope are PR or PK or PH or PM and the amino acid at C-terminal position is L or A or I or V or M, comprising a step of substituting the N-terminal residue of said epitope with an alanine.
A cryptic HLA-B*0702-restricted epitope, selected in the group consisting of APRSPLAPS (SEQ ID NO:
- 2), SPKANKEIL (SEQ ID NO:
- 3), GPKHSDCLA (SEQ ID NO:
- 4), DPRRLVQLL (SEQ ID NO:
- 1).
An immunogenic HLA-B*0702-restricted epitope, which is derived from the cryptic HLA-B*0702-restricted epitope APRSPLAPS (SEQ ID NO:
- 2), by substituting its C-terminal amino-acid with a leucine.
An immunogenic HLA-B*0702-restricted epitope, which is derived from a cryptic HLA-B*0702-restricted epitope selected in the group consisting of SPKANKEIL (SEQ ID NO:
- 3), GPKHSDCLA (SEQ ID NO:
- 4), DPRRLVQLL (SEQ ID NO:
- 1), by substituting its N-terminal amino-acid with an alanine.
A kit of parts comprising, in separate formulations, a first peptide having the sequence of a HLA-B*0702-restricted cryptic epitope, and a second peptide corresponding to its cognate HLA-B*0702-restricted immunogenic epitope.
A kit of parts comprising, in separate formulations, a first chimeric polypeptide comprising two, three or more HLA-B*0702-restricted cryptic epitopes, and a second chimeric polypeptide comprising HLA-B*0702-restricted immunogenic epitope cognate to the HLA-B*0702-restricted cryptic epitopes comprised in the first chimeric polypeptide.
21-27. (canceled)
Dependencies are inferred from the claim text.