Development of a New Viral Immunotherapeutic Approach for Hepatocellular Carcinoma

This research project in the Mayo Clinic Hepatobiliary SPORE is assessing the use of an oncolytic virus expressing an immune stimulatory gene in combination with checkpoint inhibitor antibodies in animal models and in an early-phase clinical trial. The project team is engineering a next-generation oncolytic viral platform tailored to the treatment of hepatocellular carcinoma.

This project is building on an ongoing phase I clinical trial for hepatocellular carcinoma in which oncolytic vesicular stomatitis virus expressing the immune stimulatory gene Interferon-β (IFN-β) is injected directly into liver cancers.

Project researchers have established animal models that demonstrate that the combination of a systemic checkpoint inhibitor in conjunction with an intratumorally delivered oncolytic virus can significantly improve survival outcome over either modality alone, and that survival benefit is associated with a striking improvement in antitumor Th1 memory responses.

Hypothesis

Researchers in the Mayo Clinic Hepatobiliary SPORE hypothesize that the oncolytic vesicular stomatitis virus provides a complementary mechanism of action to immune checkpoint inhibition, and that this combination can be used to effectively treat hepatocellular carcinoma.

Project aims

The aims of this research project on development of a new viral immunotherapeutic approach to hepatocellular carcinoma are to:

  • Perform a phase IB clinical study to test the combination of vesicular stomatitis virus expressing the immune stimulatory gene IFN-β in combination with the PDL1 antibody durvalumab in study participants with advanced hepatocellular carcinoma
  • Determine the optimal dosing regimens of combination checkpoint blockade therapy with oncolytic vesicular stomatitis virus expressing the immune stimulatory gene IFN-β
  • Develop a next-generation vesicular stomatitis virus platform expressing tumor-associated antigens that is specifically tailored to hepatocellular carcinoma

Project investigators

Leaders of this Hepatobiliary SPORE project are: