Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte

Int J Cancer. 1999 Jan 5;80(1):92-7. doi: 10.1002/(sici)1097-0215(19990105)80:1<92::aid-ijc18>3.0.co;2-m.

Abstract

Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy. HLA-A24 is the most frequent allele among Japanese and is also frequently present in Asians and Caucasians. We tested CEA-encoded HLA-A24 binding peptides for their capacity to elicit anti-tumor cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8+ T lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and autologous peptide-pulsed dendritic cells as antigen-presenting cells. This approach enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were capable of eliciting CTL lines that lysed tumor cells expressing HLA-A24 and CEA. The cytotoxicity to tumor cells by the CTL lines was antigen-specific since it was inhibited by peptide-pulsed cold target cells as well as by anti-class I major histocompatibility complex (MHC) and anti-CD3 monoclonal antibodies (MAbs). The antigen specificity of the 2 CTL lines was examined using several tumor cell lines of various origins and for their peptide-dose responses. The identification of these novel CEA epitopes for CTL offers the opportunity to design and develop epitope-based immunotherapeutic approaches for treating HLA-A24+ patients with tumors that express CEA.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / pharmacology
  • Asian Continental Ancestry Group / genetics
  • Carcinoembryonic Antigen / chemistry
  • Carcinoembryonic Antigen / genetics*
  • Cytotoxicity, Immunologic*
  • Dendritic Cells / immunology
  • Digestive System Neoplasms / immunology
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology
  • European Continental Ancestry Group / genetics
  • HLA-A Antigens / genetics*
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Interferon-gamma / pharmacology
  • Japan
  • Lymphoma, B-Cell / immunology
  • Melanoma / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Epitopes
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Histocompatibility Antigens Class I
  • Interferon-gamma