New peptide vaccine candidates for epithelial cancer patients with HLA-A3 supertype alleles

J Immunother. 2007 Apr;30(3):274-81. doi: 10.1097/01.cji.0000211340.88835.e7.

Abstract

We previously identified 2 cancer-associated antigens, immediate early response gene X-1 (IEX) and small GTPase (Ran), and their 5 epitopes using human leukocyte antigen (HLA)-A33-restricted and tumor-infiltrating T cells from a colon cancer patient. In this study, we examined whether or not these peptides can induce cytotoxic T lymphocytes (CTLs) in HLA-A11+ or HLA-A31+ epithelial cancer patients because the HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs as an HLA-A3 supertype family, which is widely distributed in many ethnic populations. Among them, the 2 peptides, IEX 47-56 and IEX 61-69, induced peptide-specific CTLs from peripheral blood mononuclear cells of cancer patients with the HLA-A11 and HLA-A31 alleles more efficiently than the other 3 peptides. Antibody blocking and cold inhibition experiments revealed that the cytotoxicity of peptide-induced CTLs against cancer cells was attributable to peptide-specific and CD8+ T cells. Together with our previous findings, these results indicate that the 2 IEX peptides could be appropriate vaccine candidates for HLA-A11, HLA-A31, and HLA-A33 positive epithelial cancer patients. This information could expand the chance of a peptide-based cancer vaccine for epithelial cancer patients of many ethnic populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antibodies, Blocking / pharmacology
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / immunology*
  • Apoptosis Regulatory Proteins / pharmacology
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / pharmacology
  • Carcinoma / genetics
  • Carcinoma / immunology
  • Epithelial Cells / pathology
  • HLA-A Antigens / genetics
  • HLA-A11 Antigen
  • HLA-A3 Antigen / genetics*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / immunology*
  • Membrane Proteins / pharmacology
  • Peptide Fragments / immunology*
  • Peptide Fragments / pharmacology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, Subunit / chemistry
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / pharmacology
  • ran GTP-Binding Protein / chemistry
  • ran GTP-Binding Protein / immunology*
  • ran GTP-Binding Protein / pharmacology

Substances

  • Antibodies, Blocking
  • Apoptosis Regulatory Proteins
  • Cancer Vaccines
  • HLA-A Antigens
  • HLA-A11 Antigen
  • HLA-A3 Antigen
  • HLA-A31 antigen
  • IER3 protein, human
  • Membrane Proteins
  • Peptide Fragments
  • Vaccines, Subunit
  • ran GTP-Binding Protein