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Development of highly specific oncolytic herpes virus vectors by modification of two envelope glycoproteins

Research Project

Project/Area Number 15K15144
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Virology
Research InstitutionThe University of Tokyo

Principal Investigator

Uchida Hiroaki  東京大学, 医科学研究所, 講師 (20401250)

Co-Investigator(Kenkyū-buntansha) KOJIMA MASAKI  東京薬科大学, 生命科学部, 教授 (90277252)
TAHARA HIDEAKI  東京大学, 医科学研究所, 教授 (70322071)
Project Period (FY) 2015-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords遺伝子治療 / 腫瘍溶解性ウイルス療法 / ヘルペスウイルス / 抗体 / がん
Outline of Final Research Achievements

Herpes simplex virus (HSV) vectors are promising agents for oncolytic virotherapy. We have recently reported a fully retargeted HSV platform that incorporates single-chain antibodies (scFv) into gD to mediate entry exclusively via tumor-associated antigens, including epidermal growth factor receptor (EGFR). In this study, we sought to examine whether another envelope glycoprotein, gB, could also be genetically re-engineered to interact with tumor-associated antigens. We inserted an anti-EGFR scFv or the EGF ligand into a number of different portions of gB, and found that many, but not all, of the mutated gB proteins were expressed on the cell surface. We also found that the viruses incorporating some of the mutated gB proteins retained the capability of entering cells, suggesting the potential feasibility of gB retargeting.

Report

(2 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (9 results)

All 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] University of Pittsburgh(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Development of an oncolytic HSV vector fully retargeted specifically to cellular EpCAM for virus entry and cell-to-cell spread.2016

    • Author(s)
      Shibata T, Uchida H, Shiroyama T, Okubo Y, Suzuki T, Ikeda H, Yamaguchi M, Miyagawa Y, Fukuhara T, Cohen JB, Glorioso JC, Watabe T, Hamada H, Tahara H.
    • Journal Title

      Gene Therapy.

      Volume: 印刷中 Issue: 6 Pages: 479-488

    • DOI

      10.1038/gt.2016.17

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A newly developed anti-Mucin 13 monoclonal antibody targets pancreatic ductal adenocarcinoma cells.2015

    • Author(s)
      Nishii Y, Yamaguchi M, Kimura Y, Hasegawa T, Aburatani H, Uchida H, Hirata K, Sakuma Y.
    • Journal Title

      International Journal of Oncology.

      Volume: 46 Issue: 4 Pages: 1781-1787

    • DOI

      10.3892/ijo.2015.2880

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大腸癌の遺伝子治療・ウイルス療法2015

    • Author(s)
      内田宏昭, 田原秀晃
    • Journal Title

      日本臨床

      Volume: 1077 Pages: 569-573

    • Related Report
      2015 Annual Research Report
  • [Presentation] がん細胞のみに侵入可能な標的化改変ヘルペスウイルスの開発2016

    • Author(s)
      内田宏昭
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 腫瘍細胞表面抗原を介して侵入する標的化単純ヘルペスウイルスベクターの開発2015

    • Author(s)
      城山智貴, 内田宏昭, 大久保優, 柴田智子, 福原武志, 山口美樹, Justus B. Cohen, Joseph C. Glorioso, 渡部徹郎, 濱田洋文, 田原秀晃
    • Organizer
      第7回血液疾患免疫療法研究会
    • Place of Presentation
      東京大学本郷キャンパス(東京都文京区)
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Exploration of cancer-targeting antibodies using an HSV-based screening system for development of novel HSV vectors fully retargeted to cancer cells.2015

    • Author(s)
      内田宏昭
    • Organizer
      The 21th Annual Meeting of Japan Society of Gene Therapy.
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2015-07-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] がん細胞表面抗原を介して細胞内侵入する標的化改変単純ヘルペスウイルスベクターの開発2015

    • Author(s)
      内田宏昭
    • Organizer
      第56回日本臨床ウイルス学会
    • Place of Presentation
      岡山大学鹿田キャンパス(岡山県岡山市)
    • Year and Date
      2015-06-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Remarks] 東京大学医科学研究所先端医療研究センター臓器細胞工学分野ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/sur+trans/sur+be/index.html

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-01-27  

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