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

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19181
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: The 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
• Keywords: 腫瘍溶解性ウイルス / コクサッキーウイルス

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.

Free Research Field

腫瘍溶解性ウイルス

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。