Basic research on novel oncolytic virus therapy targeting glioma initiating cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: The University of Tokyo
• Principal Investigator: IWAI Miwako 東京大学, 医科学研究所, 技術専門職員 (50396884)
• Research Collaborator: TODO Tomoki ; INO Yasushi ; MIYAZONO Kohei ; WATABE Tetsuro
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ウイルス療法 / 脳腫瘍 / がん幹細胞 / 単純ヘルペスウイルスI型

Outline of Final Research Achievements

We performed a basic research for the development of a novel oncolytic herpes simplex virus type 1 (HSV-1) targeting glioma initiating cells (GICs). Using a third generation oncolytic HSV-1, G47Δ, as the backbone, we constructed a novel oncolytic HSV-1, termed T-BMP4, by incorporating the human bone morphogenetic proteins 4 (BMP4) gene into the viral genome. T-BMP4 exhibited a potent efficacy in vitro for several GIC lines established from clinical glioma specimens. In mice intracranial GIC-tumor model, intratumoral injections with T-BMP4 significantly prolonged the survival compared with mock treatment. Further, T-BMP4 was significantly more efficacious than the control virus T-01. These results suggest that oncolytic HSV-1 armed with BMP4 exhibits enhanced therapeutic efficacy especially for GIC rich tumors, and may serve as a practical tool for the eradication of malignant glioma with high recurrence rate.

Free Research Field

医歯薬学、分子生物学