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Updated: Jan 16, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Hypothesis-generating evaluation of multi-armoured oncolytic HSV-1 (VG161) in intrahepatic cholangiocarcinoma: pooled
Yinan Shen1,2, Xinyan Jin3, Wei Song2
1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China liangtingbo@zju.edu.cn shen_yinan@zju.edu.cn shirleybai@zju.edu.cn.
Background:
Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited treatment options and poor prognosis, especially for patients who failed standard therapies.
Objective:
To explore the safety, efficacy and immunological mechanisms of the novel edition of oncolytic virus vaccination, VG161, a multiarmed oncolytic herpes simplex virus-1 expressing interleukin (IL)-12, IL-15 and a programmed death-ligand 1 antagonist, in patients with advanced ICC.
Design:
This pooled analysis integrates data from two multicentre clinical studies: a Phase I dose-escalation study and a Phase IIa exploratory study. 24 patients with advanced ICC received ultrasound-guided intratumoral injections of VG161. Multiomics analyses were performed on longitudinal tumour biopsies to evaluate immune modulation.
Results:
The oncolytic virus therapy VG161 was well tolerated and showed encouraging antitumour activity, including improved overall survival versus second-line FOLFOX chemotherapy, even though most patients received VG161 as third-line or later therapy. Notably, patients previously treated with immune checkpoint inhibitors (CPIs) experienced enhanced benefit. Multiomics profiling of longitudinal biopsies revealed significant remodelling of the immunosuppressive tumour microenvironment, with proliferated infiltration of antigen-presenting cells, CD8+ T cell activation and M2-like macrophage depletion. Single-cell and spatial transcriptomics identified epithelial and macrophage subpopulations (Epi-C2 and Macro-C1QC) as potential biomarkers of response and resistance.
Conclusion:
These early-phase findings suggest that VG161 elicits meaningful immune activation in ICC and supports further investigation. By inducing both direct oncolysis and multilayered immune activation, VG161 shows clinical benefit in a heavily pretreated population and holds promise for integration with CPI-based regimens. Validation in larger trials is warranted.
Insights
The novel oncolytic virus VG161 shows promise for advanced intrahepatic cholangiocarcinoma (ICC), improving survival and immune response. This therapy, VG161, offers hope for patients with limited options, particularly when combined with immune checkpoint inhibitors.
Area of Science:
- Oncolytic virotherapy
- Immunotherapy
- Hepatobiliary Cancers
Background:
- Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with poor outcomes, especially after standard treatments fail.
- Limited therapeutic options exist for advanced ICC patients who have exhausted conventional therapies.
Purpose of the Study:
- To evaluate the safety, efficacy, and immune mechanisms of VG161, a novel oncolytic virus therapy, in advanced ICC patients.
- VG161 is a multiarmed oncolytic herpes simplex virus-1 engineered to express IL-12, IL-15, and a PD-L1 antagonist.
Main Methods:
- Pooled analysis of Phase I and Phase IIa clinical studies involving 24 advanced ICC patients.
- Patients received ultrasound-guided intratumoral injections of VG161.
- Multiomics analyses of tumor biopsies assessed immune modulation.
Main Results:
- VG161 was well-tolerated and demonstrated encouraging anti-tumor activity, improving overall survival compared to FOLFOX chemotherapy.
- Patients previously treated with immune checkpoint inhibitors (CPIs) showed enhanced benefit from VG161 therapy.
- Multiomics revealed remodeling of the tumor microenvironment, including increased antigen-presenting cells, CD8+ T cell activation, and M2 macrophage depletion.
Conclusions:
- Early-phase findings indicate VG161 effectively activates the immune system in ICC, supporting further research.
- VG161 demonstrates clinical benefit in heavily pretreated patients by inducing oncolysis and immune activation, showing potential for combination with CPIs.
- Further validation in larger clinical trials is necessary.
