2025-04-08 浙江大学(ZJU)
Figure 1. Schematic diagram expounding the mechanism of action of oncolytic virus killing malignancies and enhancing tumor-specific immunity in TME.
<関連情報>
- https://www.zju.edu.cn/english/2025/0421/c19573a3040853/page.htm
- https://www.nature.com/articles/s41586-025-08717-5
難治性肝細胞癌に対する癌溶解ウイルスVG161 Oncolytic virus VG161 in refractory hepatocellular carcinoma
Yinan Shen,Xueli Bai,Qi Zhang,Xingmei Liang,Xinyan Jin,Zeda Zhao,Wei Song,Qian Tan,Ronghua Zhao,William Jia,Shanzhi Gu,Guoming Shi,Ziwei Zheng,Guyue Wei,Youlei Wang,Tian Fang,Yuwei Li,Zijun Wang,Zifan Yang,Sida Guo,Danni Lin,Fang Wei,Lei Wang,Xiaoli Sun,… Tingbo Liang
Nature
Abstract
Hepatocellular carcinoma remains a life-threatening malignancy with limited therapeutic options following the failure of second-line treatments1,2. Oncolytic viruses selectively replicate in and lyse cancer cells, releasing neoantigens and stimulating systemic antitumour immunity3, offering a potential therapeutic option. Here we present the results of a multicentre phase 1 clinical trial evaluating VG161, an engineered oncolytic herpes simplex virus that expresses IL-12, IL-15, IL-15Rα and a PD-1–PD-L1-blocking fusion protein4, for safety and efficacy in patients with advanced liver cancer. VG161 was well tolerated, with no dose-limiting toxicities observed, and it demonstrated promising efficacy by reshaping the tumour immune microenvironment and re-sensitizing tumours that were previously resistant to systemic treatments. Notably, we also found that patients who had previously been sensitive to checkpoint inhibitor therapy showed enhanced efficacy with VG161 treatment. Furthermore, we developed an efficacy-prediction model based on differentially expressed genes, which successfully identified patients who were likely to benefit from VG161 and predicted prolonged overall survival. These findings position VG161 as a promising third-line therapeutic option for refractory hepatocellular carcinoma. This provides a new avenue for treatment and advances the field of oncolytic virus-based immunotherapies. ClinicalTrials.gov registration: NCT04806464.
