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Chimeric antigen receptor gamma delta T cell immunotherapy for the treatment of malignant mesothelioma

Research Project

Project/Area Number 24390326
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Thoracic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

Nakajima Jun  東京大学, 医学部附属病院, 教授 (90188954)

Co-Investigator(Kenkyū-buntansha) KAKIMI Kazuhiro  東京大学, 医学部附属病院, 特任教授 (80273358)
MURAKAWA Tomohiro  東京大学, 医学部附属病院, 登録研究員 (50359626)
MATSUSHITA Hirokazu  東京大学, 医学部附属病院, 特任講師 (80597782)
SANO Atsushi  東京大学, 医学部附属病院, 登録診療員 (20569834)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywords胸膜中皮腫 / 細胞移入治療 / γδT細胞 / メソテリン / CAR / NOGマウス / 細胞傷害活性 / 抗腫瘍効果 / αβT細胞 / メソテリン特異的受容体 / NOGマウス、抗腫瘍効果 / 免疫細胞治療 / CAR / メッセンジャーRNA / エレクトロポレーション(EP)法 / ACC-Meso4 / Chimeric Antigen Receptor(CAR) / メッセンジャーRNA(mRNA)
Outline of Final Research Achievements

To develop antigen-specific immunotherapy for malignant mesothelioma, we established mesothelin-specific chimeric antigen receptor (MesoCAR) inducedγδTcells. MesoCAR mRNA was transduced into γδTcells, and optimal conditions of MesoCAR+γδTcell adoptive therapy for in vivo and in vitro mesothelioma models were investigated. Anti-tumor effects of MesoCAR+γδTcells were observed, and the anti-tumor effects were comparable to or might be better than those of MesoCAR+ αβTcells. Off-tumor/on-target toxicity to normal tissues was not seen, and the graft-versus host disease was not induced. MesoCAR+ γδTcell adoptive therapy may be an effective treatment without causing major side-effects for mesothelioma or other mesothelin-positive tumors.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (31 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (11 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 5 results,  Open Access: 2 results) Presentation (17 results) (of which Invited: 6 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Identification of Individual Cancer-Specific Somatic Mutations for Neoantigen-Based Immunotherapy of Lung Cancer.2016

    • Author(s)
      Karasaki T, Nagayama K, Kawashima M, Hiyama N, Murayama T, Kuwano H, Nitadori J, Anraku M, Sato M, Miyai M, Hosoi A, Matsushita H, Kikugawa S, Matoba R, Ohara O, Kakimi K, Nakajima J
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 11(3) Issue: 3 Pages: 324-33

    • DOI

      10.1016/j.jtho.2015.11.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Neoantigen load, antigen presentation machinery, and immune signatures determine prognosis in clear cell renal cell carcinoma.2016

    • Author(s)
      Matsushita H, Sato Y, Karasaki T, Nakagawa T, Kume H, Ogawa S, Homma Y, Kakimi K.
    • Journal Title

      Cancer Immunology Research

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Advances in personalized cancer immunotherapy.2016

    • Author(s)
      Kakimi K, Karasaki T, Matsushita H, Sugie T.
    • Journal Title

      Breast Cancer.

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cytotoxic T lymphocytes block tumor growth both by lytic activity and IFN-γ-dependent cell cycle arrest.2015

    • Author(s)
      2)Matsushita H, Hosoi A, Ueha S, Abe J, Fujieda N, Tomura M, Maekawa R, Matsushima K, Ohara O, Kakimi K.
    • Journal Title

      Cancer Immunology Research

      Volume: 3(1) Pages: 26-36

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] γδ T cell therapy for the treatment of non-small cell lung cancer2014

    • Author(s)
      Kazuhiro K, Hirokazu M, Tomohiro M, Jun N.
    • Journal Title

      Translational Lung Cancer Research

      Volume: 3(1) Pages: 23-33

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] γδ T cell therapy for the treatment of non-small cell lung cancer.2014

    • Author(s)
      Kakimi K, Matsushita H, Murakawa T, Nakajima J.
    • Journal Title

      Transl Lung Cancer Res

      Volume: 3 Pages: 23-33

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adoptive cytotoxic T lymphocyte therapy triggers a counter-regulatory immunosuppressive mechanism via recruitment of myeloid-derived suppressor cells.2014

    • Author(s)
      Hosoi A, Matsushita H, Shimizu K, Fujii SI, Ueha S, Abe J, Kurachi M, Maekawa R, Matsushima K, Kakimi K.
    • Journal Title

      Int J Cancer.

      Volume: 134 Issue: 8 Pages: 1810-22

    • DOI

      10.1002/ijc.28506

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain andthe common γ-chain.2013

    • Author(s)
      Izumi T, Kondo M, Takahashi T, Fujieda N, Kondo A, Tamura N, Murakawa T, Nakajima J, Matsushita H, Kakimi K.
    • Journal Title

      Cytotherapy

      Volume: 15(4) Issue: 4 Pages: 481-491

    • DOI

      10.1016/j.jcyt.2012.12.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] γδT細胞によるがん免疫治療2013

    • Author(s)
      垣見和宏、宮井まなみ
    • Journal Title

      実験医学増刊

      Volume: 31 Pages: 185-189

    • Related Report
      2013 Annual Research Report
  • [Journal Article] がん免疫編集機構における自然免疫系と適応免疫系の役割2013

    • Author(s)
      松下博和
    • Journal Title

      実験医学増刊

      Volume: 31 Pages: 92-99

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Ex vivo characterization of γ δ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2T cells expressing the interleukin-2 receptor β-chain and the commony -chain.2013

    • Author(s)
      Takmichi Izumi, et al.
    • Journal Title

      Cytotherapy

      Pages: 481-491

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 肺癌におけるneoantigen load、免疫チェックポイント、およびimmune signatureに関する検討2016

    • Author(s)
      唐崎 隆弘、長山 和弘、中島 淳
    • Organizer
      第13回日本免疫治療学研究会学術集会
    • Place of Presentation
      東京ガーデンパレスホテル(東京都文京区)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 既存のデータベースから抽出した遺伝子変異をターゲットとした肺癌ペプチドワクチン開発の限界について2015

    • Author(s)
      唐崎隆弘、長山和弘、川島光明、檜山紀子、村山智紀、桑野秀規、似鳥純一、安樂真樹、佐藤雅昭、垣見和宏、中島 淳
    • Organizer
      第56回 日本肺癌学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-11-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] メソテリン特異的キメラ抗原受容体発現γδT細胞を用いた養子免疫療法2015

    • Author(s)
      松下博和、中島 淳、井上雄太、長岡孝治、上羽悟史、松島綱治、垣見和宏
    • Organizer
      第7回 血液疾患免疫療法研究会学術集会(SIHDS 2015)
    • Place of Presentation
      伊藤国際学術研究センター(東京都文京区)
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] In silico prediction of neoantigen for lung cancer tarageting shared somatic mutations.2015

    • Author(s)
      Takahiro Karasaki, Kazuhiro Nagayama, Manami Miyai, Hirokazu Matsushita, Shingo Kikugawa, Ryo Matoba, Paul Horton, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
    • Organizer
      第19回日本がん免疫学会総会
    • Place of Presentation
      伊藤国際学術研究センター(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Galectin-9 and Tim-3 interaction constrains Vγ9Vδ2 T cell-based immunotherapy2015

    • Author(s)
      Takuya Takahashi, Kosuke Odaira, Kaori Kambara, Nao Fujieda, Takamichi Izumi, Yukari Kobayashi, Hirokazu Matsushiita, Kazuhiro Kakimi
    • Organizer
      第19回日本がん免疫学会総会
    • Place of Presentation
      伊藤国際学術研究センター(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 養子免疫治療におけるキメラ抗原受容体遺伝子導入ターゲット細胞としてのVγ9Vδ2T細胞2014

    • Author(s)
      松下博和、中島淳、井上雄太、村川知弘、垣見和宏
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗mesothelin-キメラ型抗原受容体導入γδTリンパ球による免疫療法の有用性2014

    • Author(s)
      井上雄太、村山智紀、此枝千尋、一瀬淳二、日野春秋、長山和弘、松下博和、似鳥純一、安樂真樹、村川知弘、垣見和宏、中島淳
    • Organizer
      第55回日本肺癌学会総会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2014-08-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Development of γδ T cell-based cancer immunotherapy2014

    • Author(s)
      垣見和宏
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      ひめぎんホール(愛媛県松山市)
    • Year and Date
      2014-08-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] がん免疫治療新時代に向けて2014

    • Author(s)
      垣見和宏
    • Organizer
      第11回東レ先端融合研究シンポジウム
    • Place of Presentation
      東レ先端融合研究所(神奈川県鎌倉市)
    • Year and Date
      2014-07-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Autologous γδT cell transfer therapy for the treatment of Solid Cancer2013

    • Author(s)
      Kazuhiro Kakimi, et al.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Vancouver, British Columbia, Canada
    • Year and Date
      2013-01-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] Killing and IFN-γ-dependent G1 cell cycle arrest is the mechanism of regulation of tumor growth by Cytotoxic T Lymphocytes.2013

    • Author(s)
      Kazuhiro Kakimi, Hirokazu Matsushita, Akihiro Hosoi, Ryuji Maekawa, and Osamu Ohara.
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Killing and IFN-γ-dependent G1 cell cycle arrest is the mechanism of regulation of tumor growth by Cytotoxic T Lymphocytes.2013

    • Author(s)
      Hirokazu Matsushita, Akihiro Hosoi, Satoshi Ueha, Jun Abe, Michio Tomura, Ryuji Maekawa, Osamu Ohara, Kazuhiro Kakimi.
    • Organizer
      21st Annual cancer research Institute International cancer
    • Place of Presentation
      New York, NY, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 癌免疫治療新時代に向けて2013

    • Author(s)
      垣見和宏
    • Organizer
      第34回癌免疫外科研究会
    • Place of Presentation
      岡山県岡山市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] クリニカルゲノミクスへの期待:がん免疫治療の見地から2013

    • Author(s)
      垣見和宏
    • Organizer
      かずさDNA 研究所/産総研 生命情報工学研究センター共催ワークショップ
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ヒトがん免疫病態の解明と免疫バイオマーカーの同定2013

    • Author(s)
      河上裕、徐明利、谷口智憲、野地しのぶ、南雲春菜、岡本正人、桜井敏晴、藤田知信、鳥越俊彦、佐藤昇志、中面哲也、垣見和宏、池田裕明、珠玖洋、奥野清隆、杉浦史哲、中山睿一、硲彰一、岡正朗、伊東恭吾
    • Organizer
      17回日本がん免疫学会総会
    • Place of Presentation
      山口県宇部市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Autologous γδT Cell Transfer Therapy for The Treatment of Cancer2013

    • Author(s)
      Kazuhiro Kakimi
    • Organizer
      第42回日本免疫学会総会/学術集会
    • Place of Presentation
      千葉県千葉市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Autologous γδT cell transfer therapy for the treatment of Solid Cancer2012

    • Author(s)
      Kazuhiro Kakimi, et al.
    • Organizer
      The 9th Catholic International Stem Cell Symposium
    • Place of Presentation
      Seoul, Korea.(招待講演)
    • Year and Date
      2012-09-15
    • Related Report
      2012 Annual Research Report
  • [Book] 医学のあゆみ20132013

    • Author(s)
      宮井まなみ、垣見和宏
    • Total Pages
      7
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2012 Annual Research Report
  • [Remarks] 免疫細胞治療学研究室のHP

    • URL

      http://immunoth.umin.jp/result/index_03.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 免疫細胞治療学講座(メディネット)ホームページ

    • URL

      http://immunoth.umin.jp/result/index_03.html

    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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