Multimodal therapy by microRNA-encoding oncolytic virus

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10970
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hiroshima University
• Principal Investigator: Kubo Tadahiko 広島大学, 医系科学研究科(医), 准教授 (70397959)
• Co-Investigator(Kenkyū-buntansha): 安達 伸生 広島大学, 医系科学研究科(医), 教授 (30294383) ; 古田 太輔 広島大学, 病院(医), 助教 (30781645) ; 坂口 剛正 広島大学, 医系科学研究科(医), 教授 (70196070)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 骨肉腫 / 腫瘍溶解性ウイルス / マイクロRNA

Outline of Final Research Achievements

Recombinant VSV expressing miRNA29a or miRNA34a or miRNA143 were generated using the established method of reverse genetics. It was examined whether the oncolytic effect on osteosarcoma cells is stronger than that of VSV. By evaluating the expression of miRNA29a, 34a, 143 in osteosarcoma cells and MSCs by RT-PCR, the expression of each miRNAs in osteosarcoma cells were significantly lower than those in MSCs. When osteosarcoma cells were infected with each recombinant viruses in vitro, miRNA expression was increased, and VSV-miRNA143 was found to have an enhanced oncolytic effect as compared with VSV. This study suggests that the newly developed VSV-miRNA is effective for the treatment of osteosarcoma.

Free Research Field

骨軟部腫瘍学

Academic Significance and Societal Importance of the Research Achievements

抗癌剤を用いた悪性腫瘍全身治療では、抵抗性や重篤な副作用など課題も多く、第三の治療法が切望されている。これまで腫瘍溶解性ウイルスである水泡性口内炎ウイルス(VSV)を骨肉腫治療に用いる研究を行ってきたが遠隔転移の完全制御と長期生存は実現できていなかった。VSVとmiRNAを組み合わせることで抗腫瘍効果を増強させた本研究結果は、悪性骨・軟部腫瘍治療に革新をもたらすのみにとどまらず、多くの癌治療に広く応用可能と考えられる。