Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin-2B in oral cancer patients

J Transl Med. 2009 Jan 6:7:1. doi: 10.1186/1479-5876-7-1.

Abstract

Background: We previously reported an HLA-A24-restricted cytotoxic T-cell epitope, Survivin-2B80-88, derived from a splice variant of survivin, survivin-2B. In this report, we show a novel HLA-A24-restricted T-cell epitope, Survivin-C58, derived from a wild type survivin, and compared their immunogenicity in oral cancer patients.

Methods: By stimulating peripheral blood lymphocytes of HLA-A24-positive cancer patients with Survivin-C58 peptide in vitro, the peptide-specific CTLs were induced. In order to compare the immunogenic potential between C58 peptide and 2B80-88 peptide, peripheral blood T-cells from thirteen HLA-A24-positive oral cancer patients were stimulated with either or both of these two peptides.

Results: Survivin-2B80-88 peptide-specific CTLs were induced from four patients, and C58 peptide-specific CTLs were induced from three out of eight patients with over stage II progression. The CTLs exerted cytotoxicity against HLA-A24-positive tumor cells. In contrast, CTL induction failed from a healthy volunteer and all four patients with cancer stage I.

Conclusion: It was indicated that a splicing variant-derived peptide and wild type survivin-derived peptide might have a comparable potency of CTL induction, and survivin targeting immunotherapy using survivin-2B80-88 and C58 peptide cocktail should be suitable for HLA-A24+ oral cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alternative Splicing
  • Animals
  • Cell Line, Tumor
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Humans
  • Immunotherapy
  • Inhibitor of Apoptosis Proteins
  • Male
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / immunology*
  • Middle Aged
  • Mouth Neoplasms / immunology*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / therapy
  • Peptides / genetics
  • Peptides / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tissue Distribution

Substances

  • BIRC5 protein, human
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Peptides
  • Survivin