Identification of HLA-A24-restricted CTL epitope from cancer-testis antigen, NY-ESO-1, and induction of a specific antitumor immune response

Clin Cancer Res. 2004 Feb 1;10(3):890-6. doi: 10.1158/1078-0432.ccr-1086-3.

Abstract

Purpose: For the development of peptide-based, cancer-specific immunotherapy, the identification of CTL epitopes from additional tumor antigens is very important. NY-ESO-1, a cancer-testis antigen, is considered to be a promising target of tumor-specific immunotherapy. Because HLA-A24-expressing individuals cover >60% in the population of Japan, we aim at identifying NY-ESO-1-encoded peptide presented by HLA-A24.

Experimental design: In our study, a HLA-A24-restricted CTL epitope was identified by using the following four-step procedure: (a) computer-based epitope prediction from the amino acid sequence of NY-ESO-1 antigen; (b) peptide-binding assay to determine the affinity of the predicted peptide with HLA-A24 molecule; (c) stimulation of primary T-cell response against the predicted peptides in vitro; and (d) testing of the induced CTLs toward various carcinoma cells expressing NY-ESO-1 antigen and HLA-A24.

Results: Of the tested peptides, effectors induced by a peptide of NY-ESO-1 at residue position 158-166 lysed three kinds of carcinoma cells expressing both NY-ESO-1 and HLA-A24. Our results indicate that peptide NY-ESO-1 (158-166) (LLMWITQCF) is a new HLA-A24-restricted CTL epitope capable of inducing NY-ESO-1-specific CTLs in vitro mediating HLA class I-restricted manner.

Conclusions: We identified a novel HLA-A24-restricted NY-ESO-1-derived epitope peptide (LLMWITQCF) that could induce specific CTLs from the peripheral blood mononuclear cells of HLA-A24(+) healthy donors. This peptide would be useful in further evaluating the clinical utility of peptide-based, cancer-specific immunotherapy against various histological tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / chemistry
  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents / pharmacology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cytokines / biosynthesis
  • DNA, Complementary / metabolism
  • Dendritic Cells / cytology
  • Epitopes*
  • HLA-A Antigens / chemistry*
  • HLA-A Antigens / metabolism
  • HLA-A24 Antigen
  • Humans
  • Immunotherapy / methods*
  • Leukocytes, Mononuclear / metabolism
  • Membrane Proteins / metabolism*
  • Neoplasms / therapy*
  • Peptides / chemistry
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / chemistry*
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Antigens
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • CTAG1B protein, human
  • Cytokines
  • DNA, Complementary
  • Epitopes
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Membrane Proteins
  • Peptides