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Research on enhancement of therapeutic efficacy based on the kinetic analysis in oncolytic virotherapy for malignant brain tumors

Research Project

Project/Area Number 20K09364
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionThe University of Tokyo

Principal Investigator

Ito Hirotaka  東京大学, 医科学研究所, 助教 (30863815)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords悪性脳腫瘍 / ウイルス療法 / 脳腫瘍
Outline of Research at the Start

がん治療用遺伝子組換え単純ヘルペスウイルスI型であるG47Δを用いた、再発膠芽腫を対象とした医師主導治験では、非常に高い治療効果が示された一方で、一部の患者で治療抵抗性を示すことが明らかとなった。実用化を間近に控え、この治療抵抗性のメカニズムの解明はウイルス療法の治療効果のさらなる向上につながることから意義が大きい。膠芽腫マウスモデルを用いて、ウイルス療法における免疫細胞の動態を解析することで治療抵抗性の機序を解明するとともに、その解析に基づいた治療介入を行うことで、治療抵抗性を克服し、幅広い患者に高い治療効果を示すウイルス療法の実現を目的とする。

Outline of Final Research Achievements

In the oncolytic virotherapy of a mouse model of brain tumor, the concomitant use of a CSF-1 receptor inhibitor was found to alter microglial dynamics, alter gene expression profiles in the tumor microenvironment, affect OV-tumor dynamics, and enhance therapeutic efficacy. We were able to accumulate basic data for further improvement of therapeutic efficacy in oncolytic virotherapy.

Academic Significance and Societal Importance of the Research Achievements

ウイルス療法における治療抵抗性機序が解明されることで、2021年に実用化され、今後さらなる発展が予想される悪性脳腫瘍に対するウイルス療法において、その治療効果を格段に向上させる可能性があるという点で学術的・社会的意義がある。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2022 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results) Book (2 results)

  • [Journal Article] Redesigned reporter gene for improved proton exchange-based molecular MRI contrast2020

    • Author(s)
      Perlman Or、Ito Hirotaka、Gilad Assaf A.、McMahon Michael T.、Chiocca E. Antonio、Nakashima Hiroshi、Farrar Christian T.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 20664-20664

    • DOI

      10.1038/s41598-020-77576-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus2020

    • Author(s)
      Mineo Marco、Lyons Shawn M.、Zdioruk Mykola、von Spreckelsen Niklas、Ferrer-Luna Ruben、Ito Hirotaka、et al
    • Journal Title

      Molecular Cell

      Volume: 78 Issue: 6 Pages: 1207-1223.e8

    • DOI

      10.1016/j.molcel.2020.05.015

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glioblastoma infiltration of both tumor- and virus-antigen specific cytotoxic T cells correlates with experimental virotherapy responses2020

    • Author(s)
      Alayo Quazim A.、Ito Hirotaka、Passaro Carmela、Zdioruk Mykola、Mahmoud Ahmad Bakur、Grauwet Korneel、Zhang Xiaoli、Lawler Sean E.、Reardon David A.、Goins William F.、Fernandez Soledad、Chiocca E. Antonio、Nakashima Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 5095-5095

    • DOI

      10.1038/s41598-020-61736-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 悪性脳腫瘍モデルに対するウイルス療法における、イメージングと生体マーカーを用いた予後解析2022

    • Author(s)
      伊藤博崇
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Book] Medical Science Digest2020

    • Author(s)
      伊藤博崇、藤堂具紀
    • Total Pages
      4
    • Publisher
      ニュー・サイエンス社
    • Related Report
      2020 Research-status Report
  • [Book] CLINICAL NEUROSCIENCE2020

    • Author(s)
      伊藤博崇、藤堂具紀
    • Total Pages
      6
    • Publisher
      中外医学社
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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