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Basic analysis for the novel immunotherapy against the gastrointestinal tumor

Research Project

Project/Area Number 15590622
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

SHIINA Shuichiro  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 助手 (70251238)

Co-Investigator(Kenkyū-buntansha) TATEISHI Keisuke  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手
KAWAKAMI Takayuki  The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員 (60376457)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsGVT / GVHD / Gastrointestinal tumor / 骨髄非破壊的末梢血造血幹細胞移植 / 細胞免疫治療 / 骨髄非破壊的末消血造血幹細胞移植(ミニ移植)
Research Abstract

The combination of allogeneic bone marrow transplantation (allo-BMT) and donor lymphocyte infusion (DLI) has been potentially a curative therapy for patients with hematological malignancies. The anti-leukemic effect is substantiated by clinical evidence and much of the therapeutic potential relates to not only the high dose of chemoradiation but also the graft-versus-leukemia (GVL) effect. In a while, the feasibility of graft-versus-tumor (GVT) effect against solid cancers has been already suspected in some clinical studies, but the efficiency and molecular mechanisms remain unclear. Here we modified the mouse two-parent F1 model established for experimental GVHD analysis to investigate the GVT effect against solid tumor. In the subcutaneously transplanted colon cancer models, allogenic donor cell infusion combined with preconditioning by irradiation was effective for inhibiting tumor formation by inducing apoptosis of tumor cells, and TRAIL dependent cytotoxic system contributed to the anti-tumor effect cooperatively with FasL system.
The gastrointestinal tract is a major target of graft-versus-host disease (GVHD), which constitutes a life-threatening complication of bone marrow transplantation. GVHD is mainly caused by the activation of donor-derived lymphocytes, in which cytokine cascades play essential roles. Since p38 MAPK has been identified as a regulator of cytokine reactions and proposed as a molecular target for anti-inflammatory therapy, we investigated the contribution of p38 to the severity of murine intestinal GVHD. Unexpectedly, p38α^<+/-> donor graft induced more acute GVHD-related mortality and more severe gut injury. In conclusion, the inhibition of p38 MARK may not be a suitable anti-inflammatory strategy for GVHD due to the associated intestinal injury.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (4 results)

All 2005 Other

All Journal Article (3 results) Publications (1 results)

  • [Journal Article] Reduced p38 Mitogen-activated Protein Kinase in Donor Grafts Accelerates Acute Intestinal Graft-versus-Host Disease in Mice2005

    • Author(s)
      大田幹, 立石敬介, 椎名秀一朗
    • Journal Title

      European journal of immunology (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reduced p38 Mitogen-activated Protein Kinase in Donor Grafts Accelerates Acute Intestinal Graft-versus-Host Disease in Mice2005

    • Author(s)
      大田幹, 立石敬介, 椎名秀一郎
    • Journal Title

      European journal of immunology 印刷中

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reduced p38 Mitogen-activated Protein Kinase in Donor Grafts Accelerates Acute Intestinal Graft-versus-Host Disease in Mice

    • Author(s)
      Ohta Miki, Keisuke Tateishi, Shuichiro Shiina
    • Journal Title

      European Journal of Immunology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 立石 敬介: "骨髄非破壊的同種幹細胞移植"肝胆膵. 46巻6号. 787-790 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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