溶瘤病毒VG161在难治性肝癌中的作用，这一成果由浙江省胰腺疾病重点实验室研究小组经过不懈努力而取得。2025年3月19日出版的《自然》杂志发表了这一最新研究成果。

在此，该课题组人员展示了一项多中心i期临床试验的结果，该试验评估了VG161在晚期肝癌患者中的安全性和有效性。VG161是一种表达IL-12、IL-15、IL-15Rα和PD-1–PD-L1阻断蛋白的工程溶瘤性单纯疱疹病毒。VG161耐受性良好，未观察到剂量限制性毒性，并且通过重塑肿瘤免疫微环境和使先前对全身治疗有抗性的肿瘤重新敏感，显示出有希望的疗效。值得注意的是，课题组还发现先前对检查点抑制剂治疗敏感的患者在接受VG161治疗后疗效增强。

此外，该课题组人员建立了一个基于差异表达基因的疗效预测模型，该模型成功地识别了可能受益于VG161的患者，并预测了延长的总生存期。这些发现表明VG161有望成为难治性肝细胞癌的三线治疗选择。这为治疗提供了新的途径，并推动了基于溶瘤病毒的免疫治疗领域的发展。

研究人员表示，肝细胞癌仍然是一种危及生命的恶性肿瘤，在二线治疗失败后，治疗选择有限。溶瘤病毒主题选择性地在癌细胞中复制和裂解，释放新抗原并刺激全身抗肿瘤免疫，提供了一种潜在的治疗选择。

附：英文原文

Title: Oncolytic virus VG161 in refractory hepatocellular carcinoma

Author: Shen, Yinan, Bai, Xueli, Zhang, Qi, Liang, Xingmei, Jin, Xinyan, Zhao, Zeda, Song, Wei, Tan, Qian, Zhao, Ronghua, Jia, William, Gu, Shanzhi, Shi, Guoming, Zheng, Ziwei, Wei, Guyue, Wang, Youlei, Fang, Tian, Li, Yuwei, Wang, Zijun, Yang, Zifan, Guo, Sida, Lin, Danni, Wei, Fang, Wang, Lei, Sun, Xiaoli, Qin, Aijun, Xie, Longshen, Qiu, Yeting, Bao, Wenqing, Rahimian, Shah, Singh, Manu, Murad, Yanal, Shang, Jianying, Chu, Min, Huang, Maoliang, Ding, Jun, Chen, Wei, Ye, Yufu, Chen, Yiwen, Li, Xiang, Liang, Tingbo

Issue&Volume: 2025-03-19

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.

DOI: 10.1038/s41586-025-08717-5

Source: https://www.nature.com/articles/s41586-025-08717-5