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

Kouichirou Tahara, Kazutoh Takesako, Alessandro Sette, Esteban Celis, Seigo Kitano, Tsuyoshi Akiyoshi

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2236-2241
Number of pages6
JournalClinical Cancer Research
Volume5
Issue number8
StatePublished - Aug 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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