Development of replication-selective oncolytic viral vector using modified mammalian orthoreovirus

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860340
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Osaka University
• Principal Investigator: KANAI YUTA 大阪大学, 微生物病研究所, 特任講師(常勤) (80506501)
• Co-Investigator(Renkei-kenkyūsha): Kobayashi Takeshi 大阪大学, 微生物病研究所 感染症国際研究センター ウイルス複製研究グループ, 特任准教授 (90324847)
• Research Collaborator: Kawagishi Takahiro 大阪大学, 微生物病研究所 感染症国際研究センター ウイルス複製研究グループ, 学振特別研究員 ; Matsuura Yoshiharu 大阪大学, 微生物病研究所 分子ウイルス分野, 教授 (50157252) ; Okamoto Toru 大阪大学, 微生物病研究所 分子ウイルス分野, 助教 (80628595)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: レオウイルス / 癌 / 遺伝子治療

Outline of Final Research Achievements

Mammalian Reovirus (MRV) has important capacity that MRV show selective oncolytic activity in cancer cells. Currently, wild type T3D-C strain, which displays significant oncolytic activity, is developed as viral oncolytic agent.
To develop improved oncolytic MRV reagent, we established reverse genetics system for T3D-C strain, the known strongest oncolytic strain. We generated recombinant RGD-MRV which has integrin-interactive RGD motif in MRV sigma1 protein to enable infection to MRV-resistant cancer cells via MRV receptor independent manner. This RGD-MRV exhibited enhanced infectivity and oncolysis of reovirus-resistant cancer cell. Next, we have generated reporter-MRV which express exogenous Luciferase (NanoLuc) transgene. Infection and replication site of Nanoluc-MRV in mice model could be monitored by in vivo imaging system (IVIS). Further, when NanoLuc-MRV were injected intravenously to human cancer xenograft mice, IVIS revealed that NanoLuc-MRV selectively infected in tumor.

Free Research Field

ウイルス学