Identification of a MAGE-2-encoded human leukocyte antigen-A24-binding synthetic peptide that induces specific antitumor cytotoxic T lymphocytes

Clin Cancer Res. 1999 Aug;5(8):2236-41.

Abstract

Because MAGE-2 gene is expressed in a wide variety of malignant tumors and HLA-A24 is the most common allele in the Japanese population and is also frequently present in Caucasians, the identification of MAGE-2-encoded peptide presented by HLA-A24 is, therefore, considered to be important in order to develop specific immunotherapy for malignant tumors using peptides as a vaccine. By using a MHC-binding assay, eight peptides derived from MAGE-2 were found to bind with sufficient affinity to the HLA-A24 molecule. When the induction of specific cytotoxic T lymphocytes (CTLs) was examined using a simplified method, the highest human lymphocyte antigen (HLA) binder (EYLQLVFGI) in these peptides was able to elicit CTLs from unseparated peripheral blood mononuclear cells in HLA-A24 healthy donors by stimulation with freshly isolated, peptide-pulsed peripheral blood mononuclear cells as antigen-presenting cells and also by using interleukin 7 and keyhole-limpet hemocyanin in a primary culture. The induced CTL could, thus, lyse HLA-A24 tumor cells expressing MAGE-2, as well as the peptide-pulsed target cells, with antigen specificity in a HLA class I-restricted manner. The identification of this peptide may, thus, be of therapeutic value in peptide-based vaccines for the treatment of several types of malignant tumors expressing MAGE-2.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic
  • Epitopes / immunology
  • Flow Cytometry
  • HLA-A Antigens / immunology*
  • HLA-A Antigens / metabolism
  • HLA-A24 Antigen
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / metabolism
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • RNA, Messenger / biosynthesis
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Epitopes
  • HLA-A Antigens
  • HLA-A24 Antigen
  • MAGEB2 protein, human
  • Neoplasm Proteins
  • Peptide Fragments
  • RNA, Messenger