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mechanisms of vasculopathy in chronic GVHD

Research Project

Project/Area Number 22K16309
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionJichi Medical University

Principal Investigator

Morita Kaoru  自治医科大学, 医学部, 助教 (20813223)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsGVHD / GVL / endothelium / cGVHD
Outline of Research at the Start

同種造血幹細胞移植後に発症する慢性移植片対宿主病(cGVHD)と移植片対白血病・リンパ腫(GVL)効果は表裏一体の関係にあり、cGVHDの治療法開発にはGVL効果を損なわない治療戦略が必要である。しかし、両者の間で標的抗原の同一性と差異性は十分にわかっていない。これまでに私たちは、HLA class IIに質的・量的に「セルフ」と異なる分子が結合したネオ・セルフがcGVHDの標的抗原になることを明らかにした。本研究では、cGVHDとGVL効果における共通のネオ・セルフを明らかにし、cGVHDの新規治療法だけでなく、腫瘍細胞のネオ・セルフを標的にする新たな癌治療の開発につなげる。

Outline of Final Research Achievements

Chronic GVHD (Graft-versus-Host Disease) is a systemic autoimmune-like complication that occurs after allogeneic transplantation, but the specific cells targeted within tissues are not well understood. This study revealed that vascular endothelial cells produce various chemokines and cytokines, which are biomarkers of chronic GVHD. These factors attract and activate immune cells locally. The production of these factors involves IFN-γ, and ROCK2 inhibitors were found to be effective in regulating this process. Furthermore, vascular endothelial cells express alloantigen/HLA class II complexes on their membranes, and some leukemia cells also exhibit these complexes. This suggests that vascular endothelial cells are involved not only in chronic GVHD but also in the Graft-versus-Leukemia (GVL) effect.

Academic Significance and Societal Importance of the Research Achievements

慢性GVHDは適切なマウスモデルがないこともあり、病態解明が十分に進んでいない。本研究によって、血管内皮細胞が慢性GVHDにおいて重要な役割を果たすことが明らかになったことで、疾患の病態生理学的メカニズムに新たな知見を提供できると考えている。また、IFN-γやROCK2阻害剤が慢性GVHDの制御に関与することが示され、今後、新たな治療戦略の開発につながる可能性がある。

Report

(2 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (11 results)

All 2024 2023

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Cost-Effectiveness of Anti-BCMA Chimeric Antigen Receptor T Cell Therapy in Relapsed/Refractory Multiple Myeloma2024

    • Author(s)
      Yamamoto Chihiro, Morita Kaoru, Kanda Yoshinobu, et.al.
    • Journal Title

      Transplantation and Cellular Therapy

      Volume: 30 Issue: 1 Pages: 118.e1-118.e15

    • DOI

      10.1016/j.jtct.2023.10.001

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fatty Acids Play a Critical Role in Mitochondrial Oxidative Phosphorylation in Effector T Cells in Graft-versus-Host Disease2024

    • Author(s)
      Nakano Hirofumi、Sato Kazuya、Izawa Junko、Takayama Norihito、Hayakawa Hiroko、Ikeda Takashi、Kawaguchi Shin-Ichiro、Mashima Kiyomi、Umino Kento、Morita Kaoru、Ito Ryoji、Ohno Nobuhiko、Tominaga Kaoru、Endo Hitoshi、Kanda Yoshinobu
    • Journal Title

      ImmunoHorizons

      Volume: 8 Issue: 3 Pages: 228-241

    • DOI

      10.4049/immunohorizons.2300115

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of CD34<sup>+</sup> cell dose on engraftment and long‐term outcomes after allogeneic bone marrow transplantation2024

    • Author(s)
      Oyama Takashi, Morita Kaoru, Kanda Yoshinobu, et.al.
    • Journal Title

      Clinical Transplantation

      Volume: 38 Issue: 4

    • DOI

      10.1111/ctr.15313

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase 2 trial of induction with dasatinib and consolidation with hyper-CVAD plus dasatinib followed by allografting for Ph-positive acute lymphoblastic leukemia in adults2024

    • Author(s)
      Oh Iekuni, Morita Kaoru, Kanda Yoshinobu, et.al.
    • Journal Title

      Leukemia Research

      Volume: 137 Pages: 107438-107438

    • DOI

      10.1016/j.leukres.2024.107438

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antibody-mediated pathogenesis of chronic GVHD through DBY/HLA class II complexes and induction of a GVL effect.2023

    • Author(s)
      Umino K, Morita K, Ikeda T, Kawaguchi SI, Nagayama T, Ito S, Minakata D, Ashizawa M, Yamamoto C, Hatano K, Sato K, Ohmine K, Fujiwara SI, Kimura SI, Kako S, Doki N, Ozawa Y, Mori Y, Eto T, Hiramoto N, Nakamae H, Kanda J, Ichinohe T, Atsuta Y, Nakasone H, Morishima S, Kanda Y.
    • Journal Title

      Blood.

      Volume: 142 Issue: 11 Pages: 1008-1021

    • DOI

      10.1182/blood.2023019799

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutational analysis of DNMT3A improves the prognostic stratification of patients with acute myeloid leukemia2023

    • Author(s)
      Wakita Satoshi, Marumo Atsushi, Morita Kaoru, et.al.
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 4 Pages: 1297

    • DOI

      10.1111/cas.15720

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Forodesine Enhances Immune Responses through Guanosine-Mediated TLR7 Activation while Preventing Graft-versus-Host Disease2023

    • Author(s)
      Ikeda Takashi、Sato Kazuya、Kawaguchi Shin-ichiro、Izawa Junko、Takayama Norihito、Hayakawa Hiroko、Umino Kento、Morita Kaoru、Matsumoto Kana、Ushijima Kentaro、Kanda Yoshinobu
    • Journal Title

      The Journal of Immunology

      Volume: 212 Issue: 1 Pages: 143-153

    • DOI

      10.4049/jimmunol.2300003

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relapsed and refractory multiple myeloma: A systematic review and network meta-analysis of the efficacy of novel therapies.2023

    • Author(s)
      Minakata D, Fujiwara SI, Yokoyama D, Noguchi A, Aoe S, Oyama T, Koyama S, Murahashi R, Nakashima H, Hyodo K, Ikeda T, Kawaguchi SI, Toda Y, Ito S, Nagayama T, Mashima K, Umino K, Morita K, Ashizawa M, Yamamoto C, Hatano K, Sato K, Ohmine K, Kanda Y.
    • Journal Title

      Br J Haematol.

      Volume: 200 Issue: 6 Pages: 694-703

    • DOI

      10.1111/bjh.18654

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early reversal of the lymphocyte‐to‐monocyte ratio after allogeneic‐hematopoietic stem cell transplantation is associated with reduced relapse and improved prognosis2023

    • Author(s)
      Nagayama Takashi, Fujiwara Shin‐ichiro, Morita Kaoru, Kanda Yoshinobu
    • Journal Title

      Clinical Transplantation

      Volume: 37 Issue: 12

    • DOI

      10.1111/ctr.15116

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] Antibody-mediated immunity to DBY/HLA class II complex formation in chronic GVHD and GVL effect2023

    • Author(s)
      森田薫、海野健斗、仲宗根秀樹、森島聡子、神田善伸
    • Organizer
      第85回日本血液学会
    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2023

    • Inventor(s)
      森田薫、神田善伸、海野健斗
    • Industrial Property Rights Holder
      森田薫、神田善伸、海野健斗
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-079282
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report

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Published: 2022-04-19   Modified: 2025-01-30  

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