Identification of a SART-1-derived peptide capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes

Int J Cancer. 1999 May 5;81(3):459-66. doi: 10.1002/(sici)1097-0215(19990505)81:3<459::aid-ijc21>3.0.co;2-6.

Abstract

We have described the SART-1 gene-encoding peptides recognized by HLA-A2601-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). We now have investigated whether SART-1 encodes peptides capable of inducing the HLA-A24-restricted CTLs. Among the 18 different peptides with HLA-A24-binding motifs, the SART-1(690-698) peptide (EYRGFTQDF) was most strongly recognized by the HLA-A24-restricted and tumor-specific CTLs established from an esophageal cancer patient. After a third stimulation in vitro, this peptide induced HLA-A24-restricted CTLs recognizing the SART-1(259)+ tumor cells in PBMCs of all HLA-A24 homozygous and the majority of HLA-A24 heterozygous cancer patients and healthy donors tested. A similar activity, induction of CTLs from PBMCs, was observed in the Saccharomyces cerevisiae-derived nonapeptide (EYRGFTPMF) that shares 7 amino acids with the SART-1(690-698) peptide. The SART-1(690-698) peptide-induced CTL activity was significantly higher in PBMCs of HLA-A24 homozygotes than in HLA-A24 heterozygotes. The CTL precursor frequency in PBMCs after a third stimulation in vitro with the SART-1(690-698) peptide was high (>1/200) in both cancer patients and healthy donors. The SART-1(690-698) peptide could thus be useful for specific immunotherapy of HLA-A24+ cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm*
  • Cell Line
  • Cytotoxicity, Immunologic
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Humans
  • Neoplasm Proteins / immunology*
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Peptide Fragments / immunology*
  • Ribonucleoproteins, Small Nuclear*
  • Saccharomyces / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Neoplasm Proteins
  • Peptide Fragments
  • Ribonucleoproteins, Small Nuclear
  • SART1 protein, human