Identification of a new MAGE-A10 antigenic peptide presented by HLA-A*0201 on tumor cells

Cancer Biol Ther. 2011 Feb 15;11(4):395-400. doi: 10.4161/cbt.11.4.14100. Epub 2011 Feb 15.

Abstract

MAGE-A antigens belong to cancer/testis (CT) antigens that are expressed in tumors but not in normal tissues with the exception of testis and placenta. Among MAGE-A antigens, MAGE-A10 is extensively expressed in various histological types of tumors, representing an attractive target for tumor immunotherapy. Cytotoxic T lymphocytes (CTLs) play a key role in anti-tumor immune responses, so the identification of CTL epitopes derived from MAGE-A10 would contribute a lot to the design of epitope-based vaccines for tumor patients. In this study, we predicted HLA-A*0201-restricted CTL epitope peptides of MAGE-A10, followed by peptide/HLA-A*0201 binding affinity and complex stability assays, and induced peptide-specific CTL immune responses. Of the selected three peptides (designated P1, P2 and P3), P1 (MAGE-A10310-318, SLLKFLAKV) could elicit peptide-specific CTLs both in vitro from HLA-A*0201-positive PBMCs and in HLA-A*0201/Kb transgenic mice. And, the induced CTLs could lyse MAGE-A10-expressing tumor cells in a HLA-A*0201-restricted fashion but not MAGE-A10-negative tumor cells. Our results demonstrate that the peptide MAGE-A10310-318 is a HLA-A*0201-restricted CTL epitope of MAGE-A10 and could serve as a target for therapeutic antitumoral vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology
  • HLA-A Antigens / immunology*
  • HLA-A Antigens / metabolism
  • HLA-A2 Antigen
  • Humans
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Peptides* / immunology
  • Peptides* / metabolism
  • Protein Binding / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • MAGE-A10 antigen
  • Neoplasm Proteins
  • Peptides
  • Interferon-gamma