2022 Fiscal Year Final Research Report

Development of diagnostic and therapeutic integrated navigation surgery using fluorescent protein-transfected reovirus.

Research Project

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Project/Area Number	20K09082
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Oita University
Principal Investigator	Etoh Tsuyoshi 大分大学, 医学部, 准教授 (00404369)
Co-Investigator(Kenkyū-buntansha)	猪股雅史大分大学, 医学部, 教授 (60315330) 山田健太郎大分大学, 医学部, 准教授 (70458280) 小川雄大大分大学, 医学部, 病院特任助教 (40733621)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	レオウイルス / 遺伝子組換え / 抗腫瘍効果 / 光線力学療法 / 近赤外蛍光
Outline of Final Research Achievements	Oncolytic reovirus selectively proliferates in cancer cells and causes cell lysis. We have shown the efficacy of wild-type reovirus on gastric cancer cell lines in basic research. In this study, we focused on near-infrared fluorescent proteins (iRFP720 and BDFP) and phototoxic red fluorescent protein (KillerRed) for intraoperative microtumor diagnosis and tumor-killing effect. iRFP720 recombinant reovirus was created and showed infection and fluorescent expression in cancer cells. BDFP recombinant reovirus was created, and its proliferation and fluorescence expression were improved. Currently, we are verifying infection of peritoneal seeding and fluorescence expression. We have also created KillerRed recombinant reovirus, and are currently writing a paper on its efficacy in adding to the tumor-killing effect of photodynamic therapy.
Free Research Field	ウイルスを用いた癌治療
Academic Significance and Societal Importance of the Research Achievements	消化器癌では根治切除が唯一完治できる治療であるが、腹膜転移とリンパ節転移は予後不良因子である。外科的切除において、微小癌遺残が再発・転移に繋がるが、それを蛍光プローブ等により可視化して発見・除去する技術が注目を浴びている。本研究ではイメージングに適した近赤外蛍光蛋白質（iRFP720及びBDFP）や、光毒性を有する赤色蛍光蛋白質（KillerRed）を発現する組換えレオウイルスを作成・検証した。これらの組換えレオウイルスは術中微小癌診断と殺癌細胞効果を同時に行うという診断治療一体型ナビゲーション手術を可能にし、消化器癌の術後生存率向上に寄与すると考えた。