MEK inhibitors selectively suppress GVHD while sparing antitumor and antiviral immunity after allogeneic hematopoietic stem cell transplantation
| Project/Area Number |
26461451
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto University (2016)
Saga University (2014-2015) |
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Principal Investigator |
Shindo Takero 京都大学, 医学研究科, 助教 (10646706)
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| Co-Investigator(Kenkyū-buntansha) |
木村 晋也 佐賀大学, 医学部, 教授 (80359794)
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| 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)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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)
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| 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） |
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| 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.
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Report
(4 results)
Research Products
(28 results)
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[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
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Journal Title
NAID
Related Report
Peer Reviewed
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[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
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Journal Title
Cancer Immunol Res
Volume: 4
Issue: 8
Pages: 644-649
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Internal Medicine
Volume: 55
Issue: 15
Pages: 2061-2064
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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[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
Int'l Joint Research
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