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Development of novel recombinant oncolytic virotherapy which has superiority in safety and antitumor efficacy

Research Project

Project/Area Number 16K19181
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

Miyamoto Shohei  東京大学, 医科学研究所, 特任助教 (20758536)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腫瘍溶解性ウイルス / コクサッキーウイルス / エンテロウイルス / ウィルス / 癌 / 遺伝子 / トランスレーショナルリサーチ
Outline of Final Research Achievements

Recently, the development of oncolytic virotherapy has been actively carried out and gathered attention. Research of enterovirus had been conducted for the understanding of its pathogenicity, particularly coxsackievirus A21 (CVA21) is one of the candidates for oncolytic virotherapy and many clinical trials have recently been underway. We previously reported that coxsackivirus B3 (CVB3), Echovirus 4 (EV4), and Poliovirus (PV) had potent oncolytic activity for cancer, and induced immunogenic cell death of CVB3-infected cells.
To development the more safety and effectively virus, we generated chimeric virus at the P1, P2 and P3 region between CVB3, CVA21, EV4 and PV.
Although some chimeras between CVA21 and PV were nonfunctional, most recombinant viruses between CVB3 and EV4 were viable, especially, EBE (EV4 with P2 region of CVB3) had higher titer than wild type EV4. These unique genomic insights could be useful for vaccine and anti-cancer development.

Academic Significance and Societal Importance of the Research Achievements

近年、腫瘍溶解性ウイルスの研究は盛んに行われており、HSVを始め多くの腫瘍溶解性ウイルスが臨床試験で検討されているが、ほとんどのウイルスは治療効果が限定的であり治療薬として不十分なものが多い。この状況を打破するため、我々は新たな腫瘍溶解性ウイルスの探索を目的に、エンテロウイルス38種類を用いた抗腫瘍活性スクリーニングから見出した候補ウイルスよりキメラウイルスを作製した。その結果、有望な腫瘍溶解性エンテロウイルスを見いだすことができた。本研究から得られた新規組換え腫瘍溶解性ウイルスは日本初のオリジナルウイルスとして、ウイルス療法の起爆剤になることを期待している。

Report

(2 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (4 results)

All 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Extremely low organ toxicity and strong antitumor activity of miR-34-regulated oncolytic coxsackievirus B3.2019

    • Author(s)
      Jia, Y., Miyamoto, S., Soda, Y., Takishima, Y., Sagara, M., Liao, J., Hirose-Yotsuya, L., Hijikata, Y., Miura, Y., Hara, K., Iwanaga, A., Ota, Y., Tani, K.
    • Journal Title

      Mol Ther Oncolytics.

      Volume: 12 Pages: 246-258

    • DOI

      10.1016/j.omto.2019.01.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KLF1 Mutation E325K Induces Cell-cycle Arrest in Erythroid Cells Differentiated from Congenital Dyserythropoietic Anemia (CDA) Patient-specific Induced Pluripotent Stem Cells.2019

    • Author(s)
      Kohara H, Utsugisawa T, Sakamoto C, Hirose L, Ogawa Y, Ogura H, Sugawara A, Aoki T, Iwasaki T, Asai T, Doisaki S, Okuno Y, Muramatsu H, Abe T, Kurita R, Miyamoto S, Sakuma T, Shiba M, Yamamoto T, Ohga S, Yoshida K, Ogawa S, Ito E, Kojima S, Kanno H, Tani K.
    • Journal Title

      Exp Hematol.

      Volume: 73 Pages: 25-37

    • DOI

      10.1016/j.exphem.2019.03.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel combination therapy for human oxaliplatin-resistant colorectal cancer using oxaliplatin and coxsackievirus A11.2018

    • Author(s)
      Wang, B., Ogata, H., Takishima, Y., Miyamoto, S., Inoue, H., Kuroda, M., Yamada, K., Hijikata, Y., Murahashi, M., Shimizu, H., Okazaki, T., Nakanishi, Y., Tani, K.
    • Journal Title

      Anticancer Res.

      Volume: 38 Issue: 11 Pages: 6121-6126

    • DOI

      10.21873/anticanres.12963

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] The current preparative status of oncolytic coxsackievirotherapy toward clinical trial.2018

    • Author(s)
      Shohei Miyamoto
    • Organizer
      第24回日本遺伝子細胞治療学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2021-01-27  

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