Induction of antitumor cytotoxic T lymphocytes from the peripheral blood mononuclear cells of cancer patients using HLA-A2-restricted MAGE-3 peptide in vitro

Tatsuo Fujie, Fumiaki Tanaka, Masaki Mori, Kazutoh Takesako, Keizo Sugimachi, Tsuyoshi Akiyoshi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

As the basis for the application of MAGE antigens to therapeutic use, the induction of peptide-specific CTLs has been investigated by the stimulation of peripheral blood mononuclear cells (PBMCs) with antigenic peptides derived from MAGE genes. However, the cross-reactivity of the peptide-induced CTLs to the target cells endogenously presenting the MAGE epitope, especially in cancer patients, remains controversial, despite the use of complicated manipulations. Because we recently developed a new simplified method to induce peptide-specific CTLs that killed MAGE expressing tumor cells from the PBMCs of a healthy donor, we examined the induction of specific CTLs by stimulation of PBMCs with HLA-A2-restricted MAGE-3 peptide in HLA-A2+ cancer patients whose tumors expressed MAGE-3 by using the simple method. The CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells and by using interleukin 7 and keyhole limpet hemocyanin for the primary culture. All CTLs induced from the PBMCs of four cancer patients tested could thus lyse the HLA-A2 target cells pulsed with the peptide, and moreover, two of the CTLs were also able to kill HLA-A2 tumor cells expressing MAGE-3 in a HLA class I and A2-restricted manner. Therefore, these findings seem to indicate that HLA-A2-restricted MAGE-3 peptide may be potentially useful for specific immunotherapy in cancer patients.

Original languageEnglish
Pages (from-to)2425-2430
Number of pages6
JournalClinical Cancer Research
Volume3
Issue number12 I
Publication statusPublished - Dec 1 1997

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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