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Novel cancer therapy using microRNA-regulated oncolytic viruses targeting cancer stem cells

Research Project

Project/Area Number 24300340
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Clinical oncology
Research InstitutionTottori University

Principal Investigator

Nakamura Takafumi  鳥取大学, 医学(系)研究科(研究院), 准教授 (70432911)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2013: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords癌 / ウイルス療法 / トランスレーショナルリサ ーチ / 遺伝子治療 / バイオテクノロジー / トランスレーショナルリサーチ / トランスレーションリサーチ
Outline of Final Research Achievements

Oncolytic viruses are promising therapeutic agents for cancer and are currently under clinical investigation. The virotherapy is novel strategy that viruses infect and replicate within tumor cells, directly lysing and killing them.
In this study, we have developed that microRNA (miRNA) regulation enables tumor-specific viral replication by altering the expression of a targeted viral gene of an attenuated vaccinia virus vaccine strain. We used miRNA-based gene regulation to suppress B5R expression through let-7, a miRNA that plays important roles in cancer stem cells through the downregulation of let-7 expression. The miRNA-regulated vaccinia virus (MDVV) achieved efficient viral replication and oncolysis in cancer cells, but elimination of unwanted replication and associated toxicity in normal cells in vivo. Furthermore, the MDVV armed with IL-12 enhanced its anti-tumor effects.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (27 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (13 results) (of which Invited: 2 results) Book (1 results) Remarks (7 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] ワクシニアウイルス2016

    • Author(s)
      中村 貴史
    • Journal Title

      遺伝子医学MOOK

      Volume: 30

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 腫瘍特異的に増殖する遺伝子組換えワクシニアウイルス2016

    • Author(s)
      中村 貴史
    • Journal Title

      実験医学

      Volume: 34 Pages: 31-37

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Combined Cytolytic Effects of a Vaccinia Virus Encoding a Single Chain Trimer of MHC-I with a Tax-Epitope and Tax-Specific CTLs on HTLV-I-Infected Cells in a Rat Model2014

    • Author(s)
      Ohashi T, Nakamura T, Kidokoro M, Zhang X, Shida H
    • Journal Title

      BioMed Research International.

      Volume: 2014 Pages: 902478-902478

    • DOI

      10.1155/2014/902478

    • NAID

      120005434503

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antibody neutralization of retargeted measles viruses2014

    • Author(s)
      Lech PJ, Pappoe R, Nakamura T, Russell SJ
    • Journal Title

      Virology

      Volume: 454-455 Pages: 237-246

    • DOI

      10.1016/j.virol.2014.01.027

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coxsackievirus B3 Is an Oncolytic Virus with Immunostimulatory Properties that Is Active Against Lung Adenocarcinoma2012

    • Author(s)
      Miyamoto S, Inoue H, Nakamura T, Yamada M, Sakamoto C, Urata Y, Okazaki T, Marumoto T, Takahashi A, Takayama K, Nakanishi Y, Shimizu H, Tani K
    • Journal Title

      Cancer Research

      Volume: (掲載確定)(印刷中) Issue: 10 Pages: 2609-2621

    • DOI

      10.1158/0008-5472.can-11-3185

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 難治性がんを標的破壊する遺伝子組換えワクシニアウイルスによる全身性がんウイルス療法の開発2015

    • Author(s)
      中村 貴史
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Tumor-specific, replication-competent vaccinia virus for systemic oncolytic virotherapy2015

    • Author(s)
      Nakamura T
    • Organizer
      The 21st Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Year and Date
      2015-07-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 純和製ワクシニアウイルスを用いた難治がんに対するウイルス療法の開発2015

    • Author(s)
      中村 貴史
    • Organizer
      第23回遺伝子治療推進産学懇話会
    • Place of Presentation
      京都大学東京オフィス(東京都)
    • Year and Date
      2015-04-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] がん治療に生きたウイルスを利用する~ウイルス感染・増殖の制御に基づくウイルス療法の開発~2014

    • Author(s)
      中村 貴史
    • Organizer
      第10回 霊長類医科学フォーラム
    • Place of Presentation
      文部科学省研究交流センター(つくば市)
    • Year and Date
      2014-11-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Tumor-specific, replication-competent and stealth vaccinia virus for systemic oncolytic virotherapy2014

    • Author(s)
      Motomu Nakatake , Takafumi Nakamura
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] MicroRNA regulation of viral replication for oncolytic virothrapy2013

    • Author(s)
      Nakamura T
    • Organizer
      The 2nd Meeting on RNA and Biofunctions-ASIA Study "RNA Biofunctions and Viruses"
    • Place of Presentation
      ホテルレオパレス博多(福岡)
    • Year and Date
      2013-01-09
    • Related Report
      2012 Annual Research Report
  • [Presentation] Systemic cancer therapy with MDVy a combined miKNA.-regulated and thymidine kinase-deleted oncolytic vaccinia virus2012

    • Author(s)
      Nakamura T
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] マイクロRNAによって制御されるウイルスベクターの開発2012

    • Author(s)
      中村貴史
    • Organizer
      第14回日本RNA学会年会
    • Place of Presentation
      北大学百周年記念会館(仙台)
    • Year and Date
      2012-07-18
    • Related Report
      2012 Annual Research Report
  • [Presentation] SYSTEMIC ONCOLYTIC VIROTHERAPY WITH TUMOR-SPECIFIC REPLICATING VACINIA VIRUSES2012

    • Author(s)
      Nakamura T
    • Organizer
      The 18th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      ホテル熊本テルサ(熊本)
    • Year and Date
      2012-06-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] Systemic cancer virotherapy with MDW, a combined miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus2012

    • Author(s)
      Nakamura T
    • Organizer
      The 15th Annual Meeting of American Society of Gene & Cell Therapy
    • Place of Presentation
      Pennsylvania Convention Center (Philadelphia, USA)
    • Year and Date
      2012-05-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] Safety profile, tumor selectivity and oncolytic effects after systemic administration of oncolytic vaccinia virus MDVV

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Masato Yamane, Motomu Nakatake, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] SYSTEMIC CANCER VIROTHERAPY WITH MDVV, A COMBINED miRNA-REGULATED AND THYMIDINE KINASE-DELETED ONCOLYTIC VACCINIA VIRUS

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Masato Yamane, Motomu Nakatake, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      The 19th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      岡山(岡山コンベンションセンター)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Systemic cancer virotherapy with MDVV, a combined miRNA-regulated and thymidine kinase-deleted oncolytic vaccinia virus

    • Author(s)
      Naoyoshi Nitta, Nao Okada, Ikumi Goto, Motomu Nakatake, Masato Yamane, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      The Seventh International Meeting On Replicating Oncolytic Virus Therapeutics
    • Place of Presentation
      Quebec City, Canada(Chateau Frontenac)
    • Related Report
      2013 Annual Research Report
  • [Book] 臨床・創薬利用が見えてきたmiRcroRNA「miRNA制御ウイルスによるがん細胞特異的治療法の開発」の項2012

    • Author(s)
      中村貴史
    • Total Pages
      6
    • Publisher
      株式会社メディカルドウ
    • Related Report
      2012 Annual Research Report
  • [Remarks] 研究内容紹介

    • URL

      http://www.med.tottori-u.ac.jp/integbio/522/1198.html

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Remarks] がんナビ

    • URL

      http://medical.nikkeibp.co.jp/leaf/all/cancernavi/report/201301/528660_3.html

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Remarks] ウイルスで新しいがん療法の開発をめざす

    • URL

      http://ganshien.umin.jp/research/main/nakamura/index.html

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Remarks] 研究内容紹介

    • URL

      http://www.med.tottori-u.ac.jp/integbio/522/1198.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] ウイルスで新しいがん療法の開発をめざす

    • URL

      http://ganshien.umin.jp/public/research/main/nakamura/

    • Related Report
      2013 Annual Research Report
  • [Remarks] がんナビ

    • URL

      http://medical.nikkeibp.co.jp/leaf/all/cancernavi/report/201301/528660_3.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://ganshien.umin.jp/public/research/main/nakamura/

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 分裂促進因子活性化タンパク質キナーゼ依存性組換えワクシニアウイルス(MD-RVV)及びその使用2013

    • Inventor(s)
      中村貴史
    • Industrial Property Rights Holder
      中村貴史
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-22
    • Related Report
      2013 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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