Multimodal therapy by microRNA-encoding oncolytic virus

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 骨肉腫 / 腫瘍溶解性ウイルス / マイクロRNA / 腫瘍溶解ウイルス / 悪性腫瘍 / マイクロＲＮＡ / microRNA

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.

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。

Research Products

• [Journal Article] Novel Near-Infrared Fluorescence-Guided Surgery With Vesicular Stomatitis Virus for Complete Surgical Resection of Osteosarcomas in Mice. (2019)
  • Author(s): Sakuda T, Kubo T, Johan MP, Furuta T, Sakaguchi T, Nakanishi M, Ochi M, Adachi N.
  • Journal Title: J Orthop Res. Volume: Epub ahead of print] Issue: 5 Pages: 1192-1201
  • DOI: 10.1002/jor.24277
  • Peer Reviewed
• [Presentation] Tumor-suppressor microRNA導入遺伝子組み換え腫瘍溶解性ウイルスの開発 (2019)
  • Author(s): 作田智彦、久保忠彦、古田太輔、安達伸生
  • Organizer: 第34回日本整形外科学会基礎学術集会
• [Presentation] Novel near-infrared fluorescence-guided surgery with vesicular stomatitis virus for complete surgical resection of osteosarcomas in mice (2019)
  • Author(s): Tomohiko Sakuda, Tadahiko Kubo, Muhammad Petrus Johan, Taisuke Furuta, Mitsuo Ochi, Nobuo Adachi
  • Organizer: 19th Grand Round Musculoskeletal Oncology (Indonesia)
• [Presentation] Comprehensive approach of fluorescence-guided resection combined with systemic virotherapy by VSV (2019)
  • Author(s): 作田智彦、久保忠彦、古田太輔、Muhammad Petrus Johan、安達伸生
  • Organizer: 第52回日本整形外科骨・軟部腫瘍学術集会
• [Presentation] Novel Near-Infrared Fluorescence-Guided Surgery With Vesicular Stomatitis Virus for Complete Surgical Resection of Osteosarcomas in Mice. (2019)
  • Author(s): Sakuda T, Kubo T, Johan MP, Furuta T, Sakaguchi T, Nakanishi M, Ochi M, Adachi N.
  • Organizer: 19th Ground Round of Musculoskeletal Oncology
  • Int'l Joint Research