Efficacy of third-generation oncolytic herpes simplex virus type 1 for advanced hepatocellular carcinoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kansai Medical University
• Principal Investigator: KON Masanori 関西医科大学, 医学部, 教授 (70225605)
• Co-Investigator(Kenkyū-buntansha): KAIBORI Masaki 関西医科大学, 医学部, 准教授 (30333199) ; FUJISAWA Junichi 関西医科大学, 医学部, 教授 (40181341) ; TODO Tomoki 東京大学, 医科学研究所, 教授 (80272566)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 増殖型遺伝子組換えウィルス / 単純ヘルペス英ルス / 抗腫瘍免疫 / 肝臓がん

Outline of Final Research Achievements

The use of recombinant viruses which kill tumor cells selectively in the course of viral replication is called an oncolytic virus therapy. G47Δ is a third-generation oncolytic herpes simplex virus type 1 (HSV-1) that has triple genetic modifications in the viral genome, and has already been used in clinical studies. Deletions in the γ34.5 gene and inactivation of the ICP6 gene make the virus replicate efficiently and selectively in tumor cells, and the deletion in α47 gene efficiently induces tumor cell specific immune responses. T-01 has a similar genetic structure to G47Δ. Antitumor effect of T-01 was evaluated in this study using HCC cell lines. In cytotoxicity assays in vitro, all 11 HCC cell lines tested were susceptible to T-01. T-01 was tested in vivo using 4 HCC cell lines in subcutaneous and orthotopic tumor models in nude mice. In both models, intratumoral inoculation of T-01 inhibited tumor growth efficiently compared with mock inoculation.

Free Research Field

消化器外科学