# Project 4: Immunovirotherapy

> **NIH NIH P50** · MAYO CLINIC ROCHESTER · 2022 · $253,206

## Abstract

PROJECT 4 – PROJECT SUMMARY
Hepatocellular carcinoma (HCC) is the second most frequent cause of death from cancer and a lack of
effective therapeutic options has led to a 5-year survival rate below 12%. Our group has conducted extensive
preclinical characterization of engineered Vesicular Stomatitis Virus (VSV) as an oncolytic platform and has
demonstrated it to be a highly effective immunotherapeutic agent for the treatment of cancer. We have
established murine models which demonstrate that the combination of systemic checkpoint blockade in
conjunction with an intratumorally delivered oncolytic virus can significantly improve survival outcome over
either modality alone. In addition to the oncolytic effects of VSV, we developed this platform as a potent
vaccine vector that is capable of breaking tolerance to tumor-associated antigens (TAAs) in several mouse
tumor models. In the current proposal, we will build on an ongoing Phase I clinical trial for HCC in which
oncolytic VSV expressing the immune stimulatory gene Interferon-β (IFN-β) is injected directly into liver
cancers, and on our pre-clinical data supporting combinatorial therapy with an immune checkpoint inhibition
strategy. The overall hypothesis of the current project is that oncolytic VSV provides a complementary
mechanism of action to immune checkpoint inhibition. The combination of VSV- IFN-β with durvalumab (anti-
PD-L1) will be tested in a Phase IB clinical study in patients with advanced HCC (Aim 1). Using both murine
models of HCC, we we will further refine dosing regimens of rational, mechanism-based, combinations of
multiple checkpoint blockade antibodies with VSV-IFN-β (Aim2). Using murine HCC models, will identify and
validate novel HCC TAAs that we will target with VSV immunotherapy (Aim 3). Overall, these studies will
provide insight into the design of optimized combination therapy and lead to a series of new clinical trials for
the treatment this disease for which few effective conventional therapies currently exist.

## Key facts

- **NIH application ID:** 10468832
- **Project number:** 5P50CA210964-05
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Richard G. Vile
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $253,206
- **Award type:** 5
- **Project period:** 2018-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468832

## Citation

> US National Institutes of Health, RePORTER application 10468832, Project 4: Immunovirotherapy (5P50CA210964-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468832. Licensed CC0.

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