Development of oncolytic virus therapy that can cure malignant brain tumors via modification of tumor microenvironment

2017 Fiscal Year Final Research Report

• Project/Area Number: 26253073
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: The University of Tokyo
• Principal Investigator: Todo Tomoki 東京大学, 医科学研究所, 教授 (80272566)
• Co-Investigator(Renkei-kenkyūsha): INO Yasushi 東京大学, 医科学研究所, 准教授 (50372371) ; FUKUHARA Hiroshi 東京大学, 医学部附属病院, 准教授 (20292948)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 脳腫瘍 / ウイルス療法 / がん幹細胞

Outline of Final Research Achievements

Herpes simplex virus type 1 (HSV-1) can be genetically engineered to create oncolytic HSV-1 that can replicate selectively in and kill cancer cells. This project aimed to develop innovative oncolytic virus therapy that can cure malignant brain tumors. In order to target cancer stem cells, we created oncolytic HSV-1 that expresses TGF-β inhibitor or BMP4, a factor that inhibits the stemness of cancer stem cells. Further, to confer a high replication capability even in cancer stem cell-rich tumors or benign brain tumors, we created several oncolytic HSV-1 using tumor-specific promoters. Among newly created, armed oncolytic HSV-1 with a function to modify the brain tumor microenvironment, the one expressing anti-VEGF antibody showed an efficient antitumor activity without causing the tumor swelling that usually occurs after intratumoral virus administration, proving to be highly useful for the treatment of brain tumors.

Free Research Field

脳神経外科