Induction of CD8 T-cell Responses Restricted to Multiple HLA Class I Alleles in a Cancer Patient by Immunization With a 20-mer NY-ESO-1f (NY-ESO-1 91-110) Peptide

Int J Cancer. 2013 Jan 15;132(2):345-54. doi: 10.1002/ijc.27682. Epub 2012 Jul 11.

Abstract

Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Clinical Trials, Phase I as Topic
  • Epitope Mapping
  • Genes, MHC Class I*
  • Humans
  • Immunotherapy, Active*
  • Leukocytes, Mononuclear / immunology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Peptide Fragments / immunology*
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • NY-ESO-1 protein, human (91-110)
  • Peptide Fragments