Identification of Lck-derived peptides applicable to anti-cancer vaccine for patients with human leukocyte antigen-A3 supertype alleles

Br J Cancer. 2007 Dec 17;97(12):1648-54. doi: 10.1038/sj.bjc.6604071. Epub 2007 Nov 27.

Abstract

The identification of peptide vaccine candidates to date has been focused on human leukocyte antigen (HLA)-A2 and -A24 alleles. In this study, we attempted to identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to HLA-A11(+), -A31(+), or -A33(+) cancer patients, because these HLA-A alleles share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is preferentially expressed in metastatic cancer. Twenty-one Lck-derived peptides were prepared based on the binding motif to the HLA-A3 supertype alleles. They were first screened for their recognisability by immunoglobulin G (IgG) in the plasma of prostate cancer patients, and the selected candidates were subsequently tested for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A3 supertype(+) cancer patients. As a result, four Lck peptides were frequently recognised by IgGs, and three of them - Lck(90-99), Lck(449-458), and Lck(450-458) - efficiently induced peptide-specific and cancer-reactive CTLs. Their cytotoxicity towards cancer cells was mainly ascribed to HLA class I-restricted and peptide-specific CD8(+) T cells. These results indicate that these three Lck peptides are applicable to HLA-A3 supertype(+) cancer patients, especially those with metastasis. This information could facilitate the development of peptide-based anti-cancer vaccine for patients with alleles other than HLA-A2 and -A24.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • HLA-A3 Antigen / genetics*
  • Humans
  • Immunoglobulin G / analysis
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / immunology*
  • Male
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Peptides*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Cancer Vaccines
  • HLA-A3 Antigen
  • Immunoglobulin G
  • Peptides
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)