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Clinical development of the novel oncolytic coxsackievirus B3 targeting malignant tumors

Research Project

Project/Area Number 23240133
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical oncology
Research InstitutionKyushu University

Principal Investigator

TANI Kenzaburo  九州大学, 生体防御医学研究所, 教授 (00183864)

Co-Investigator(Renkei-kenkyūsha) SHIMIZU Hiroyuki  国立感染症研究所, ウイルス第2部, 室長 (90270644)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥49,140,000 (Direct Cost: ¥37,800,000、Indirect Cost: ¥11,340,000)
Fiscal Year 2013: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2012: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2011: ¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
Keywords腫瘍溶解性ウイルス / コクサッキーウイルスB群3型 / miRNA / 顆粒球マクロファージ刺激因子 / ウイルス製剤製造 / 一般毒性試験 / GM-CSF / 腫瘍溶解ウイルス / 医薬品医療機器総合機構 / 一般毒性試 / GMP準拠 / 担癌マウスモデル / ウイルス製造 / 腫瘍溶解性ウイルス療法 / コクサッキーウイルス / GMP / 顆粒球マクロファージコロニー刺激因子 / microRNA / コクサッキーウイルス(CV)B3 / 密度勾配遠心法 / miRNA相補配列挿入CVB3 / 遺伝子改変CVB3 / miR-1 / miR-217 / CVB3精製
Outline of Final Research Achievements

Oncolytic viruses are characterized by self-replicating and tumor killing capacity, and have emerged as a promising treatment platform for cancer therapy. We previously carried out the screening of approximately 40 enterovirus strains and found that CVB3 possessed specific oncolytic activity against cell lines of human lung cancer, malignant pleural mesothelioma and breast cancer. In this study, two experiments were performed for the development of the novel oncolytic coxsackievirus B3 therapy. (1) To overcome CVB3-related organ toxicities, we constructed a novel recombinant CVB3-miRT by genetically incorporating two distinct normal tissue-specific miRNA target sequences into the CVB3 genome. We next constructed CVB3 inserting GM-CSF gene (CVB3-GM-CSF) to improve anti-tumor immunity. (2) For the purpose of producing CVB3 reagent under Good Manufacturing Practice (GMP), we developed mass production method using GMP grade reagents and instruments.

Report

(4 results)
  • 2014 Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (27 results)

All 2013 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results) Presentation (16 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] A versatile drug delivery system using streptavidin-tagged pegylated liposomes and biotinylated biomaterials2013

    • Author(s)
      Chen MH, Tojo A, et al.
    • Journal Title

      Int J Pharm.

      Volume: 454 Issue: 1 Pages: 478

    • DOI

      10.1016/j.ijpharm.2013.06.031

    • URL

      https://localhost/en/publications/62553a47-43bd-4138-83c7-6c23ba9fba69

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of PTEN tumor suppressor promotes the generation of induced pluripotent stem cells.2013

    • Author(s)
      Liao J, Marumoto T, Yamaguchi S, Okano S, Takeda N, Sakamoto C, Kawano H, Nii T, Miyamoto S, Nagai Y, Okada M, Inoue H, Kawahara K, Suzuki A, Miura Y and Tani K
    • Journal Title

      Molecular Therapy

      Volume: in press Issue: 6 Pages: 1242-1250

    • DOI

      10.1038/mt.2013.60

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments.2013

    • Author(s)
      Inoue, H., Tani ,K.
    • Journal Title

      Cell Death Differ.

      Volume: 21 Issue: 1 Pages: 39-49

    • DOI

      10.1038/cdd.2013.84

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor effect of chondroitin sulfate-coated ternary granulocyte macro phage-colony-stimulating factor plasmid complex for ovarian cancer2012

    • Author(s)
      Katsuyuki Hamada, 他
    • Journal Title

      JOURNAL OF GENE MEDICINE

      Volume: 14 Issue: 2 Pages: 120-127

    • DOI

      10.1002/jgm.1647

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coxsackievirus B3 Is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma.2012

    • Author(s)
      Miyamoto,S.
    • Journal Title

      Cancer Res.

      Volume: 72 Pages: 2609-2621

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Absence of LTB4/BLT1 axis facilitates generation of mouse GM-CSF-induced long-lasting antitumor immunologic memory by enhancing innate and adaptive immune systems.2012

    • Author(s)
      Yokota,Y.
    • Journal Title

      Blood.

      Volume: 120 Issue: 17 Pages: 3444-3454

    • DOI

      10.1182/blood-2011-10-383240

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coxsackievirus B3 Is an Oncolytic Virus with Immunostimulatory Properties that Is Active Against Lung Adenocarcinoma2012

    • Author(s)
      Shohei Miyamoto, et al
    • Journal Title

      Cancer Research

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor effect of chondroitin sulfate-coated ternary granulocyte macrophage-colony-stimulating factor plasmid complex for ovarian cancer2012

    • Author(s)
      Hamada K, et al
    • Journal Title

      J Gene Med

      Volume: 14 Pages: 120-127

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene therapy for oral squamous cell carcinoma with IAI.3B promoter-driven oncolytic adenovirus-infected carrier cells2011

    • Author(s)
      Zhang T, et al
    • Journal Title

      Oncol Rep

      Volume: 25 Pages: 795-802

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] MicroRNA-targeted coxsackievirus B3 infection markedly reduces its toxicity without losing its original oncolytic activity.2013

    • Author(s)
      Shohei Miyamoto, Hiroyuki Inoue, Miyako Sagara, Beibei Wang, Koichi Takayama, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      Therapeutics Discovery Symposium Asia Small RNAs to Stem Cells & Epigenetic Reprogramming Asia-2013 Meeting On ‘RNA Regulation to Delivery, Programming to Pluripotency & Therapeutics’
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-11-25
    • Related Report
      2013 Annual Research Report
  • [Presentation] MicroRNA-regulated coxsackievirus B3 abrogates its pathogenicity retaining oncolytic activity.2013

    • Author(s)
      Shohei Miyamoto, Hiroyuki Inoue, Miyako Sagara, Beibei Wang, Koichi Takayama, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      The 23rd Hot Spring Harbor International Symposium, Recent Advances in Stem Cell Biology 2013
    • Place of Presentation
      Fukuoka
    • Year and Date
      2013-11-04
    • Related Report
      2013 Annual Research Report
  • [Presentation] Infection with Echovirus 4 elicits potent oncolytic activity against cisplatin-resistant esophageal carcinoma.2013

    • Author(s)
      Hiroyuki Inoue, Keisuke Yasunari, Beibei Wang, Shohei Miyamoto, Koichi Takayama, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-03
    • Related Report
      2013 Annual Research Report
  • [Presentation] CVB3 infection displays different oncolytic activities against cancer stem cells and cancer cells undergoing EMT.2013

    • Author(s)
      Miyako Sagara, Hiroyuki Inoue, Shohei Miyamoto, Chika Sakamoto, Yuki Nakano, Koichi Takayama, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-03
    • Related Report
      2013 Annual Research Report
  • [Presentation] MicroRNA-targeted coxsackievirus B3 infection markedly reduces its pathogenicity retaining oncolytic activity.2013

    • Author(s)
      Shohei Miyamoto, Hiroyuki Inoue, Miyako Sagara, Beibei Wang, Koichi Takayama, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-03
    • Related Report
      2013 Annual Research Report
  • [Presentation] Differential susceptibility of cancer stem cells and cancer cells undergoing epithelial-mesenchymal transition to oncolysis by CVB3 infection.2013

    • Author(s)
      Miyako Sagara, Hiroyuki Inoue, Shohei Miyamoto, Chika Sakamoto, Yuki Nakano, Koichi Takayama, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      第19回日本遺伝子治療学会
    • Place of Presentation
      岡山
    • Year and Date
      2013-07-04
    • Related Report
      2013 Annual Research Report
  • [Presentation] Infection with dual microRNA-targeted coxsackievirus B3 abrogates its pathogenicity retaining oncolytic activity.2013

    • Author(s)
      Shohei Miyamoto, Hiroyuki Inoue, Miyako Sagara, Beibei Wang, Koichi Takayama, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      第19回日本遺伝子治療学会
    • Place of Presentation
      岡山
    • Year and Date
      2013-07-04
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dual microRNA-regulated oncolytic coxsackievirus B3 infection displays antitumor activity with attenuated pathogenicity in mice.2013

    • Author(s)
      Shohei Miyamoto, Hiroyuki Inoue, Miyako Sagara, Beibei Wang, Koichi Takayama, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      The 16th Annual Meeting of American Society of Gene and Cell Therapy
    • Place of Presentation
      Salt Lake City, UT
    • Year and Date
      2013-05-15
    • Related Report
      2013 Annual Research Report
  • [Presentation] CVB3 infection elicits potent oncolytic activity against lung cancer stem cells.2013

    • Author(s)
      Miyako Sagara, Hiroyuki Inoue, Shohei Miyamoto, Chika Sakamoto, Yuki Nakano, Koichi Takayama, Hiroyuki Shimizu Yoichi Nakanishi, Kenzaburo Tani
    • Organizer
      The 16th Annual Meeting of American Society of Gene and Cell Therapy.
    • Place of Presentation
      Salt Lake City, UT
    • Year and Date
      2013-05-15
    • Related Report
      2013 Annual Research Report
  • [Presentation] 肺癌幹細胞を標的とした新規遺伝子改変麻疹腫瘍溶解性ウイルス療法2013

    • Author(s)
      Hiroyuki Inoue, Keisuke Yasunari, Yumiko Matsumura, Kaname Nosaki, Shohei Miyamoto, Koichi Takayama, Yoichi Nakanishi, and Kenzaburo Tani
    • Organizer
      第53回日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2013-04-19
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dual microRNA-regulated oncolytic coxsackievirus B3 infection displays antitumor activity with attenuated pathogenicity in mice.2013

    • Author(s)
      Miyamoto, S.
    • Organizer
      American Society of Gene & Cell Therapy
    • Place of Presentation
      Salt Lake City, Utah, U.S.
    • Related Report
      2012 Annual Research Report
  • [Presentation] Coxsackievirus B3 is an immunostimulatory oncolytic virus active against lung adenocarcinoma.2012

    • Author(s)
      Miyamoto, S.
    • Organizer
      American Association for Cancer Research
    • Place of Presentation
      Chicago, IL, U.S.
    • Related Report
      2012 Annual Research Report
  • [Presentation] Coxsackievirus B3 is an oncolytic virus with immunostimulatory properties that is active against lung adenocarcinoma.2012

    • Author(s)
      Miyamoto, S.
    • Organizer
      第7回研究所ネットワーク国際シンポジウム
    • Place of Presentation
      仙台, 日本
    • Related Report
      2012 Annual Research Report
  • [Presentation] Coxsackievirus B3 is an immunostimulatory oncolytic virus active against lung adenocarcinoma.2012

    • Author(s)
      Miyamoto, S.
    • Organizer
      第18回日本遺伝子治療学会
    • Place of Presentation
      熊本, 日本
    • Related Report
      2012 Annual Research Report
  • [Presentation] Large-Scale Screening Identifies Coxsackievirus B3 (CVB3) as a Promising Oncolytic Virotherapy Agent against Non-Small Cell Lung Cancer2011

    • Author(s)
      Hiroyuki Inoue, et al
    • Organizer
      European Society of Gene and Cell Therapy
    • Place of Presentation
      Brighton, UK
    • Related Report
      2011 Annual Research Report
  • [Presentation] Coxsackievirus B3 is an immunostimulatory oncolytic virus active against lung adenocarcinoma2011

    • Author(s)
      Shohei Miyamoto, et al
    • Organizer
      American Association for Cancer Research Annual Meeting
    • Place of Presentation
      Chicago, Illinois (USA)
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] RECOMBINANT COXACKIEVIRUS2013

    • Inventor(s)
      谷 憲三朗
    • Industrial Property Rights Holder
      谷 憲三朗
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-04-17
    • Related Report
      2013 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 医薬組成物2012

    • Inventor(s)
      谷 憲三朗
    • Industrial Property Rights Holder
      九州大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-04-19
    • Related Report
      2012 Annual Research Report
    • Overseas

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Published: 2011-04-06   Modified: 2019-07-29  

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