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Tumor-specific and Systemic Oncolytic Vaccinia Virus for Novel Cancer Therapy

Research Project

Project/Area Number 26640103
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
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) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords癌 / ウイルス療法 / 遺伝子治療 / 抗腫瘍免疫 / 免疫回避 / がん / トランスレーショナルリサーチ / バイオテクノロジー
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 focus on highly attenuated vaccinia virus which was used for small pox vaccine. However, the vaccinia virus still has property of partial replication in normal cells. Therefore, the vaccinia virus has genetically been engineered in order to not only completely inhibit pathogenic viral replication in normal cells without impairing its therapeutic replication in tumor cells, but also 1) improve viral tumor-homing through regulation of viral morphogenesis and infection and 2) enhance anti-tumor immunity via control of the biological immune response in the tumor microenvironment. Thus, the recombinant oncolytic vaccinia virus achieved tumor-specific and systemic anti-tumor effects in mouse tumor models.

Academic Significance and Societal Importance of the Research Achievements

現行の治療法に対して極めて高い抵抗性を示し、容易に他臓器に転移する難治性進行癌に対する新規治療法の確立が望まれている。学術的意義は、宿主の免疫を逃れながら血中を介して全身に伝播できるワクシニアウイルス独自の特性を利用し、動物実験においてウイルスの腫瘍集積性の向上を実証したことや、癌免疫療法との併用による抗癌効果の増強に成功したことにある。社会的意義は、癌特異的かつ全身的な効果を併せ持つ癌ウイルス療法の確立を目指した本研究を起点に、本成果が新たながん治療法開発の第一歩となったことにある。

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (22 results)

All 2016 2015 2014 Other

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (5 results) Patent(Industrial Property Rights) (3 results)

  • [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
      2015 Research-status 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 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Presentation] Tumor-targeted and armed oncolytic vaccinia virus for systemic virotherapy2016

    • Author(s)
      Nakamura T
    • Organizer
      第75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
      2016-10-08
    • Related Report
      2016 Annual Research Report
  • [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
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Enhancing tumor specificity and therapeutic index of oncolytic vaccinia virus through deletions of both VGF and O1 protein genes2015

    • Author(s)
      Nakatake M, Yamane M, Parada R, Horita K, Okazaki M, Hasegawa K, Miyara A, Fujiwara K, Kurosaki H, 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
      2015-07-25
    • Related Report
      2015 Research-status Report
  • [Presentation] Identification of host factors required for enhancing replication and spread of oncolytic vaccinia virus2015

    • Author(s)
      Horita K, Nakatake M, Goto I, Yamane M, Okazaki M, Parada R, Kurosaki H, 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
      2015-07-25
    • Related Report
      2015 Research-status Report
  • [Presentation] mor-specific, replication-competent vaccinia virus for systemic oncolytic Nakamura T 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
      2015 Research-status Report
  • [Presentation] Deletions of both vaccinia growth factor and O1 protein genes enhance therapeutic index of oncolytic vaccinia virus2015

    • Author(s)
      Nakatake M, Yamane M, Horita K, Okazaki M, Roxana Parada R, Hajime Kurosaki H, Nakamura T
    • Organizer
      9th International Conference on Oncolytic Viruses As Cancer Therapeutics
    • Place of Presentation
      Boston Park Plaza Hotel(Boston, USA)
    • Year and Date
      2015-06-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [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
      2015 Research-status 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 Research-status 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 Research-status Report
  • [Presentation] DELETIONS OF BOTH VACCINIA GROWTH FACTOR AND O1 PROTEIN GENES ENHANCE THERAPEUTIC INDEX OF ONCOLYTIC VACCINIA VIRUS2014

    • Author(s)
      Naoyoshi Nitta, Ikumi Goto, Motomu Nakatake, Masato Yamane, Kosuke Horita, Hajime Kurosaki and Takafumi Nakamura
    • Organizer
      The 20th Annual Meeting of Japan Society of Gene Therapy
    • Place of Presentation
      東京慈恵会医科大学(東京都)
    • Year and Date
      2014-08-08
    • Related Report
      2014 Research-status Report
  • [Presentation] Deletions of both vaccinia growth factor and O1 protein genes enhance therapeutic index of oncolytic vaccinia virus2014

    • Author(s)
      Ikumi Goto, Naoyoshi Nitta, Motomu Nakatake, Nao Okada, Masato Yamane, Hajime Kurosaki, Takafumi Nakamura
    • Organizer
      The Seventeenth Annual Meeting of the American Society of Gene & Cell Therapy
    • Place of Presentation
      Marriott Wardman Park(Washington, DC)
    • Year and Date
      2014-05-21
    • Related Report
      2014 Research-status Report
  • [Remarks] 研究内容紹介

    • URL

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

    • Related Report
      2016 Annual Research Report 2015 Research-status Report 2014 Research-status Report
  • [Remarks] がんナビ

    • URL

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

    • Related Report
      2016 Annual Research Report 2015 Research-status Report 2014 Research-status Report
  • [Remarks] ウイルスで新しいがん療法の開発をめざす

    • URL

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

    • Related Report
      2016 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
      2016 Annual Research Report 2015 Research-status 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
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 外来遺伝子発現ワクシニアウイルスの製造方法2016

    • Inventor(s)
      中村貴史、中武 大夢、黒崎 創、堀田享佑
    • Industrial Property Rights Holder
      鳥取大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-138712
    • Filing Date
      2016-07-13
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] ワクシニアウイルスの増殖・伝搬を増強する宿主制御因子2015

    • Inventor(s)
      中村 貴史、堀田 享佑、黒﨑 創、 中武 大夢
    • Industrial Property Rights Holder
      鳥取大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-145153
    • Filing Date
      2015-07-22
    • Related Report
      2015 Research-status 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2014

    • Inventor(s)
      中村 貴史
    • Industrial Property Rights Holder
      国立大学法人 鳥取大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-11-20
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2020-03-30  

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