Identification of squamous cell carcinoma antigen-derived peptides having the capacity of inducing cancer-reactive CTLs in HLA-A24+ cancer patients

Int J Oncol. 2006 Sep;29(3):577-87.

Abstract

Squamous cell carcinoma antigen (SCCA) is a useful marker for SCCs. In this study, we attempted to identify SCCA-derived peptides that could be applied in the development of specific immunotherapy for HLA-A24+ cancer patients with SCC or non-SCC. A variety of SCC and non-SCC lines were examined for their expression of SCCA mRNA using quantitative PCR. SCCA protein expression in cancer tissues was investigated by immunohistochemical staining. Thereafter, SCCA-derived peptide candidates were prepared based on their binding motifs to HLA-A24 molecules. Among these peptides, SCCA-derived peptides that were frequently recognized by humoral immunity were further tested for their ability to induce cancer-reactive cytotoxic T lymphocytes (CTLs) from the peripheral blood mononuclear cells of HLA-A24+ patients with SCC or non-SCC. As a result, the majority of SCC lines and tissues were positive for SCCA both at mRNA and protein levels. By contrast, non-SCC cancer tissues hardly expressed it at the protein level, although adenocarcinoma cell lines partly expressed it at the mRNA level. Four SCCA-derived peptides were frequently recognized by immunoglobulin G of both SCC and non-SCC cancer patients. Among these peptides, both the SCCA(112-120) and SCCA(215-224) peptides were found to effectively induce peptide-specific CTLs toward HLA-A24+ SCCA+ cancer cells from the peripheral blood mononuclear cells of both SCC and non-SCC cancer patients. Two newly identified SCCA-derived peptides with the ability to induce CTL activity in both SCC and non-SCC cancer patients may be applicable to specific immunotherapy for HLA-A24+ cancer patients with SCC, but not those with non-SCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neoplasm / immunology
  • Antigens, Neoplasm / immunology*
  • Biomarkers, Tumor / immunology*
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Humans
  • Immunoenzyme Techniques
  • Immunoglobulin G / blood
  • Neoplasms / immunology*
  • Neoplasms, Squamous Cell / immunology*
  • Peptide Fragments / immunology*
  • Serpins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Immunoglobulin G
  • Peptide Fragments
  • Serpins
  • squamous cell carcinoma-related antigen