• Open Access

An efficient method to prepare T cell receptor gene-transduced cytotoxic T lymphocytes type 1 applicable to tumor gene cell-therapy

Authors

  • Takemasa Tsuji,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Kenji Chamoto,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Hiromi Funamoto,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Akemi Kosaka,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Junko Matsuzaki,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Hiroyuki Abe,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Keishi Fujio,

    1. Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113–0033
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  • Kazuhiko Yamamoto,

    1. Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113–0033
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  • Toshio Kitamura,

    1. Division of Cellular Therapy, Institute of Medical Science, University of Tokyo, 4–6–1 Shirokanedai, Minato-ku, Tokyo 108–8639
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  • Yuji Togashi,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Toshiaki Koda,

    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
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  • Takashi Nishimura

    Corresponding author
    1. Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060–0815
      To whom correspondence should be addressed. E-mail: tak24@imm.hokudai.ac.jp
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To whom correspondence should be addressed. E-mail: tak24@imm.hokudai.ac.jp

Abstract

Genes encoding 2C T cell receptor (TCR) α, β chains from H-2b-re-stricted Ld-specific CD8+ cells were successfully transduced into polyclonally activated CD8+ cells by retroviral modification to generate antigen-specific cytotoxic T lymphocytes (CTL). Antigen-nonspecific CD8+ T cells polyclonally expanded in the presence of interleukin (IL)-2, Th1 cytokines (interferon (IFN)-γ and IL-12) and anti-IL-4 monoclonal antibody showed neither cytokine production nor cytotoxicity in response to Ld-expressing P815 tumor cells. However, 2C-TCR gene-modified CD8+ T cells exhibited both IFN-γ production and cytotoxicity in response to P815 tumor cells. The antitumor activity of TCR gene-modified Tc1 cells was also demonstrated in vivo by Winn's assay. Thus, we have developed an efficient method to induce TCR gene-modified antigen-specific Tc1 cells that exhibit antitumor activity both in vitro and in vivo. (Cancer Sci 2003; 94: 389–393)

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