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Generation of specific antitumor reactivity by the stimulation of spleen cells from gastric cancer patients with MAGE-3 synthetic peptide
Authors:Tatsuo Fujie  Fumiaki Tanaka  Kouichirou Tahara  Jian Li  Shinji Tanaka  Masaki Mori  Hiroaki Ueo  Kazutoh Takesako  Tsuyoshi Akiyoshi
Institution:(1) Department of Surgery, Medical Institute of Bioregulaiton, Kyushu University, Beppu 874, Japan, JP;(2) Department of Surgery, Oita Prefectural Hospital, Oita 870, Japan, JP;(3) Biotechnology Research Laboratories, Takara Shuzo Co. Ltd., Otsu, Shiga, Japan, JP;(4) Kyushu Central Hospital, 3-23-1, Shiobaru, Minamiku, Fukuoka 815-8588, Japan Fax:+81-92-541-4540, JP
Abstract:The induction of cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using MAGE peptide has been investigated in order to use MAGE antigens immunotherapeutically. We therefore developed a simplified method for inducing peptide-specific CTL that kill tumor cells expressing MAGE from the PBMC of either healthy donors or even cancer patients. Since the spleen is a major lymphoid organ, we used a simple method to examine the capacity of spleen cells to generate MAGE-specific CTL by in vitro stimulation with MAGE peptide in gastric cancer patients. The CTL responses could thus be induced from unseparated spleen cells in HLA-A2 patients with gastric carcinoma expressing MAGE-3 by stimulating these cells with autologous spleen cells pulsed with HLA-A2-restricted MAGE-3 peptide as antigen-presenting cells and by using keyhole limpet hemocyanin and interleukin-7 for the primary culture. The induced CTL were thus able to lyse HLA-A2-positive carcinoma cells transfected with MAGE-3 and expressing MAGE-3, as well as the target cells pulsed with the peptide, in an HLA-class-I or -A2-restricted manner. Since MAGE-specific CTL could be induced from the spleen cells of gastric cancer patients, the spleen appears to play an important role in either clinical tumor vaccination or the treatment of cancer patients by adoptive immunotherapeutic approaches using the MAGE peptide. Received: 3 December 1998 / Accepted: 30 March 1999
Keywords:Cytotoxic T lymphocyte  MAGE  Antigenic peptide  Spleen cell  Cancer patient
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