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Investigation of the role of virus-specific stem cell-like memory T-cells in the patients with ATL and their therapeutic application

Research Project

Project/Area Number 18K07292
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TANAKA YUKIE  東京医科歯科大学, 統合研究機構, 助教 (10814197)

Co-Investigator(Kenkyū-buntansha) 小林 誠一郎  東京大学, 医科学研究所, 助教 (70376622)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsHTLV-1 / 幹細胞様メモリーT細胞 / HLA-A24 / HTLV-1 Tax / ステムセルメモリーT細胞 / シングルセル解析 / 成人T細胞性白血病 / 免疫学
Outline of Final Research Achievements

In this study, we analyzed stem cell memory T cells (TSCMs) of HTLV-1 Tax-CTLs. The results showed that TSCMs of Tax-CTLs, although rare, are present in the peripheral blood of HTLV-1 carriers and have very strong reactivity to Tax antigens in the in vitro experiments, and that various Tax-CTL memory clones source TSCMs, especially Tax-CTLs shared by HLA-A24 positive HTLV-1 infected individuals, are preferentially differentiated and proliferated from TSCM. It is strongly suggested that TSCMs of shared Tax-CTLs are promoted to differentiate and proliferate within HTLV-1 carriers, allowing for continuous surveillance of virus growth as dominant memory Tax-CTLs for a long period of time.

Academic Significance and Societal Importance of the Research Achievements

Tax-CTLの幹細胞様T細胞がHTLV-1キャリア末梢血中に長期間存在すること、またそれらがTax抗原に対して極めて強い反応性を発揮し、メモリーTax-CTLの供給源であることを明らかにした。本研究の成果は、ATL発症抑制機構にTax-CTL幹細胞様T細胞が非常に重要であることを示したが、今後、自己血中のTax-CTL幹細胞様T細胞の増殖法を確立することで、日本人に最も多いHLA-A24陽性HTLV-1感染者を対象にした持続的CTL効果が期待できる幹細胞様T細胞の特性を活かした細胞療法の開発への貢献が予想される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Viral loads and profile of the patients infected with SARS‐CoV‐2 Delta, Alpha, or R.1 variants in Tokyo2021

    • Author(s)
      Tani‐Sassa Chihiro、Iwasaki Yumi、Ichimura Naoya、Nagano Katsutoshi、Takatsuki Yuna、Yuasa Sonoka、Takahashi Yuta、Nakajima Jun、Sonobe Kazunari、Nukui Yoko、Takeuchi Hiroaki、Tanimoto Kousuke、Tanaka Yukie、Kimura Akinori、Tohda Shuji
    • Journal Title

      Journal of Medical Virology

      Volume: 94 Issue: 4 Pages: 1707-1710

    • DOI

      10.1002/jmv.27479

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SARS‐CoV‐2 R.1 lineage variants that prevailed in Tokyo in March 20212021

    • Author(s)
      Nagano Katsutoshi、Tani‐Sassa Chihiro、Iwasaki Yumi、Takatsuki Yuna、Yuasa Sonoka、Takahashi Yuta、Nakajima Jun、Sonobe Kazunari、Ichimura Naoya、Nukui Yoko、Takeuchi Hiroaki、Tanimoto Kousuke、Tanaka Yukie、Kimura Akinori、Tohda Shuji
    • Journal Title

      Journal of Medical Virology

      Volume: 93 Issue: 12 Pages: 6833-6836

    • DOI

      10.1002/jmv.27240

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a Unique T Cell Receptor Gene-Transferred Tax-Redirected T Cell Immunotherapy for Adult T Cell Leukemia2020

    • Author(s)
      Kawamura Koji、Tanaka Yukie、Nakasone Hideki、Ishihara Yuko、Kako Shinichi、Kobayashi Seiichiro、Tanaka Yuetsu、Ohmori Tsukasa、Uchimaru Kaoru、Okamoto Sachiko、Mineno Junichi、Shiku Hiroshi、Nishimura Satoshi、Kanda Yoshinobu
    • Journal Title

      Biology of Blood and Marrow Transplantation

      Volume: 26 Issue: 8 Pages: 1377-1385

    • DOI

      10.1016/j.bbmt.2020.04.006

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of multivirus-specific T cells by a single stimulation of peripheral blood mononuclear cells with a peptide mixture using serum-free medium2018

    • Author(s)
      NISHIYAMA-FUJITA YURIKO、KAWANA-TACHIKAWA AI、ONO TOSHIAKI、TANAKA YUKIE、KATO TAKAFUMI、HESLOP HELEN E.、MORIO TOMOHIRO、TAKAHASHI SATOSHI
    • Journal Title

      Cytotherapy

      Volume: 20 Issue: 9 Pages: 1182-1190

    • DOI

      10.1016/j.jcyt.2018.05.009

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HTLV-I感染により誘導されるウイルス抗原特異的幹細胞様メモリーT細胞の解析.2020

    • Author(s)
      田中ゆきえ、小林誠一郎、佐藤知雄、山野嘉久、神田善伸、内丸薫、森尾友宏.
    • Organizer
      第12回日本血液疾患免疫療法学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Comprehensive genetic analysis revealed myeloid/natural killer (NK) cell precursor acute leukemia as a novel distinctive leukemia entity2020

    • Author(s)
      Akira Nishimura, Kazuaki Yokoyama, Chika Yamagishi, Toshihiko Imamura, Takuya Naruto, Yukie Tanaka,Tomohiro Morio, et al.
    • Organizer
      63rd American Society of Hematology (ASH) 2020 Annual Meeting
    • Related Report
      2020 Research-status Report
  • [Presentation] 造血細胞移植後難治性ウイルス感染症に対するHLA半合致以上血縁ドナー由来複数ウイルス特異的T細胞療法2019

    • Author(s)
      藤田由利子、立川(川名)愛、田中ゆきえ、Helen E Heslop、加藤節史、岡本圭祐、河野ゆり、辻彩子、草野純、柳町昌克、森尾友宏、高橋聡
    • Organizer
      第41回日本造血細胞移植学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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