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MEK inhibitors selectively suppress GVHD while sparing antitumor and antiviral immunity after allogeneic hematopoietic stem cell transplantation

Research Project

Project/Area Number 26461451
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKyoto University (2016)
Saga University (2014-2015)

Principal Investigator

Shindo Takero  京都大学, 医学研究科, 助教 (10646706)

Co-Investigator(Kenkyū-buntansha) 木村 晋也  佐賀大学, 医学部, 教授 (80359794)
Co-Investigator(Renkei-kenkyūsha) OKADA Seiji  熊本大学, 医学研究科, 教授 (50282455)
KUBOTA Yasushi  佐賀大学, 医学部, 講師 (60570413)
TAWARA Isao  三重大学, 医学部, 助教 (80378380)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords造血幹細胞移植 / 移植片対宿主病 / 抗腫瘍免疫 / 抗ウイルス免疫 / MEK阻害剤 / 免疫抑制剤 / 移植片対腫瘍効果 / 移植片対宿主病(GVHD)
Outline of Final Research Achievements

We investigated the roles of MEK inhibitors in regulation of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) effects after allogeneic hematopoietic stem cell transplantation. We confirmed that a MEK inhibitor trametinib suppresses GVHD while sparing GVT effects in several different murine bone marrow transplant models. Meanwhile, the calcineurin inhibitor tacrolimus abrogated GVT effects, which confirmed the priority of trametinib. These results were published as a research article in JCI Insight in 2016 July, and were widely broadcasted. Currently, we are concentrating to design and start a clinical trial in humans with trametinib.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (28 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Peer Reviewed: 11 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (5 results)

  • [Int'l Joint Research] マイアミ大学シルベスター癌センター(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] マイアミ大学シルベスター癌センター(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Elderly patients with chronic myeloid leukemia benefit from a dasatinib dose as low as 20 mg.2017

    • Author(s)
      Itamura H, Kubota Y, Shindo T, Ando T, Kojima K, Kimura S
    • Journal Title

      Clin Lymph Myeloma Leuk

      Volume: 印刷中 Issue: 6 Pages: 370-374

    • DOI

      10.1016/j.clml.2017.02.023

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Persistent Gastrointestinal Angiodysplasia in Heyde’s syndrome after aortic valve replacement.2017

    • Author(s)
      Akutagawa T, Shindo T*, Yamanouchi K, Hayakawa M, Ureshino H, Tsuruoka N, Sakata Y, Shimoda R, Noguchi R, Furukawa K, Morita S, Iwakiri R, Kimura S, Matsumoto M, Fujimoto K
    • Journal Title

      Intern Med

      Volume: 印刷中

    • NAID

      130006078531

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic myelogenous leukemia and NK cell immunity.2017

    • Author(s)
      Ureshino H, Shindo T, Tanaka H, Kimura S
    • Journal Title

      Rinsho Ketsueki

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation in adult T-cell leukemia.2016

    • Author(s)
      Fuji S, Shindo T
    • Journal Title

      Stem Cell Investig

      Volume: 3 Pages: 70-70

    • DOI

      10.21037/sci.2016.09.13

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The MEK inhibitor trametinib separates murine Graft-versus-Host Disease from Graft-versus-Tumor Effects.2016

    • Author(s)
      Itamura H, Shindo T*, Tawara I, Kubota Y, Kariya R, Okada S, Komanduri KV, Kimura S
    • Journal Title

      JCI Insight

      Volume: 1 Issue: 10

    • DOI

      10.1172/jci.insight.86331

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effector regulatory T cells reflect the equilibrium between antitumor immunity and autoimmunity in adult T cell leukemia.2016

    • Author(s)
      Ureshino H, Shindo T*, Nishikawa H, Watanabe N, Watanabe E, Satoh N, Kitaura K, Kitamura H, Doi K, Nagase K, Kimura H, Samukawa M, Kusunoki S, Miyahara M, Shin-I T, Suzuki R, Sakaguchi S, Kimura S
    • Journal Title

      Cancer Immunol Res

      Volume: 4 Issue: 8 Pages: 644-649

    • DOI

      10.1158/2326-6066.cir-15-0303

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Domino-Style Cerebral Bleeding in a Patient With Immune Thrombocytopenic Purpura2016

    • Author(s)
      北村浩晃、進藤岳郎、薬師寺祐介、吉原麻里、久保田寧、野口智之、木村晋也
    • Journal Title

      JAMA Neurology

      Volume: 73 Issue: 4 Pages: 474-475

    • DOI

      10.1001/jamaneurol.2015.4508

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subdural Hematoma Associated with Dasatinib and Intrathecal Methotrexate Treatment in Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia2016

    • Author(s)
      Ureshino H, Nishioka A, Kojima K, Kizuka H, Sano H, Shindo T, Kubota Y, Ando T, Kimura S
    • Journal Title

      Internal Medicine

      Volume: 55 Issue: 18 Pages: 2703-2706

    • DOI

      10.2169/internalmedicine.55.6966

    • NAID

      130005414849

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rituximab-induced Acute Thrombocytopenia in High Tumor Burden Follicular Lymphoma2016

    • Author(s)
      Ureshino H, Nishioka A, Kojima K, Suzuki M, Kizuka H, Sano H, Shindo T, Kubota Y, Ando T, Kimura S
    • Journal Title

      Internal Medicine

      Volume: 55 Issue: 15 Pages: 2061-2064

    • DOI

      10.2169/internalmedicine.55.6140

    • NAID

      130005254817

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 成人T細胞白血病(ATL)の診断と治療2016

    • Author(s)
      進藤岳郎
    • Journal Title

      ライフライン21 がんの先進医療

      Volume: 23 Pages: 26-28

    • Related Report
      2016 Annual Research Report
  • [Journal Article] "Coexistence of ALK- anaplastic large cell lymphoma and CD4+ T-cell large granular lymphocytic leukemia "2015

    • Author(s)
      Kazuharu Kamachi1, Noriyasu Fukushima, Toshihiko Ando, Ken-ichi Sato, Koichi Ohshima, Masako Yokoo, Takero Shindo, Yasushi Kubota, Kensuke Kojima, Shinya Kimura
    • Journal Title

      Ann Hematol

      Volume: 94 Issue: 3 Pages: 539-540

    • DOI

      10.1007/s00277-014-2176-z

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] T-cell characterization using multicolor flow cytometry after allogeneic hematopoietic stem-cell transplantation.2014

    • Author(s)
      Fuji S, Shindo T
    • Journal Title

      Journal of Clinical Oncology

      Volume: 32 Pages: 1859-1860

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] TCR Repertoire, Effector Regulatory T cells and KIR Genotyping Uncover Immunological Dynamics in Mogamulizumab-treated ATL2017

    • Author(s)
      Shindo T, Kusunoki Y, Kitaura K, Nishikawa H, Watanabe N, Ureshino H, Miyahara M, Watanabe T, Sueoka E, Espinoza LJ, Takami A, Ichinohe T, Suzuki R, Tanaka H, Saji H, Kimura S
    • Organizer
      The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
    • Place of Presentation
      東京都
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Administration of tocilizumab and etanercept for severe cytokine release syndrome (CRS) with thrombotic microangiopathy after HLA-haploidentical allogeneic peripheral blood stem cell transplantation.2017

    • Author(s)
      木塚遥菜、進藤岳郎、安藤寿彦、佐野晴彦、久保田寧、小島研介、木村晋也
    • Organizer
      第39回日本造血細胞移植学会総会
    • Place of Presentation
      松江市
    • Year and Date
      2017-03-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 次世代シークエンサーを用いたTCRレパトア解析はモガムリズマブによる細胞性免疫の再構築を可視化する2016

    • Author(s)
      進藤岳郎
    • Organizer
      日本HTLV-1学会学術集会
    • Place of Presentation
      鹿児島市
    • Year and Date
      2016-08-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] The MEK inhibitor trametinib selectively suppresses GVHD, while sparing GVT and antiviral immunity.2016

    • Author(s)
      Shindo T
    • Organizer
      The 7th Japanese Society of Hematology (JSH) International Symposium (Plenary Session)
    • Place of Presentation
      淡路島夢舞台
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The MEK inhibitior Trametinib selectively suppresses GVHD, while sparing GVT effects and antiviral immunity.2016

    • Author(s)
      進藤岳郎
    • Organizer
      第7回日本血液学会国際シンポジウム
    • Place of Presentation
      淡路市「夢舞台」国際会議場
    • Year and Date
      2016-05-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The MEK inhibitior Trametinib selectively suppresses GVHD, while sparing GVT effects.2015

    • Author(s)
      板村英和、進藤岳郎、俵功、刈谷龍昇、岡田誠治、木村晋也
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢市
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 成人T細胞白血病に対するモガムリズマブの効果は活性型NK細胞受容体とリガンドのマッチングによって予測できる可能性がある2015

    • Author(s)
      進藤岳郎、楠木靖史、嬉野博志、宮原正晴、渡邊達郎、末岡榮三朗、森脇祐司、吉田真一郎、一戸辰夫、Luis J Espinoza、高見昭良、田中秀則、佐治博夫、木村晋也
    • Organizer
      第24回日本組織適合性学会大会
    • Place of Presentation
      水戸市
    • Year and Date
      2015-09-10
    • Related Report
      2015 Research-status Report
  • [Presentation] The MEK inhibitior Trametinib selectively suppresses Graft-versus-Host Disease (GVHD), while sparing Graft-versus-Tumor (GVT) effects.2015

    • Author(s)
      板村英和、進藤岳郎、久保田寧、木村晋也
    • Organizer
      がん分子標的治療学会学術集会
    • Place of Presentation
      松山市
    • Year and Date
      2015-06-11
    • Related Report
      2015 Research-status Report
  • [Presentation] The MEK inhibitor trametinib selectively suppresses GHVD, while sparing GVT effects.2015

    • Author(s)
      Hidekazu Itamura, Takero Shindo, Isao Tawara, Ryusho Kariya, Seiji Okada, Krishna V Komanduri, Shinya Kimura
    • Organizer
      ASBMT/CIBMTR BMT Tandem Meetings
    • Place of Presentation
      San Diego, CA USA
    • Year and Date
      2015-02-11 – 2015-02-15
    • Related Report
      2014 Research-status Report
  • [Remarks] 骨髄移植の免疫異常 皮膚がん薬が効果 佐賀大研究

    • URL

      https://mainichi.jp/articles/20160708/ddp/012/040/009000c

    • Related Report
      2016 Annual Research Report
  • [Remarks] 京都大学医学部附属病院 血液・腫瘍内科ウェブサイト(近日掲載予定)

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 佐賀大学医学部附属病院 血液・呼吸器・腫瘍内科ウェブサイト

    • URL

      http://www.saga-hor.jp/main/171.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] http://saga-hor.jp/main/171.html

    • Related Report
      2015 Research-status Report
  • [Remarks] MEK阻害剤を用いた、同種造血幹細胞移植後のGVHDおよびGVL/GVTの制御

    • URL

      http://www.saga-hor.jp/main/171.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2022-02-16  

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