Oncolytic virus VG161 in refractory hepatocellular carcinoma

Area of Science:

• Oncolytic virotherapy
• Immunotherapy
• Hepatocellular carcinoma research

Background:

• Hepatocellular carcinoma (HCC) has limited treatment options after second-line therapy failure.
• Oncolytic viruses offer a potential therapeutic strategy by targeting cancer cells and stimulating anti-tumor immunity.

Purpose of the Study:

• To evaluate the safety and efficacy of VG161, an engineered oncolytic herpes simplex virus, in patients with advanced liver cancer.
• To assess VG161's potential as a third-line treatment for refractory HCC.

Main Methods:

• A multicenter phase 1 clinical trial was conducted to assess VG161.
• VG161 is an oncolytic herpes simplex virus engineered to express IL-12, IL-15, IL-15Rα, and a PD-1-PD-L1-blocking fusion protein.
• An efficacy-prediction model based on gene expression was developed.

Main Results:

• VG161 was well-tolerated with no observed dose-limiting toxicities.
• The treatment demonstrated promising efficacy, reshaping the tumor immune microenvironment and re-sensitizing resistant tumors.
• Patients previously sensitive to checkpoint inhibitors showed enhanced efficacy with VG161.
• The prediction model successfully identified patients likely to benefit and predicted prolonged survival.

Conclusions:

• VG161 is a safe and promising third-line therapeutic option for refractory hepatocellular carcinoma.
• VG161 advances the field of oncolytic virus-based immunotherapies.
• The efficacy-prediction model aids in patient selection for VG161 treatment.