# Oncolytic virus therapeutic responses occur from changes in the glioblastoma immune microenvironment

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $416,647

## Abstract

Abstract
Glioblastoma (GBM) is a fatal brain cancer that recurs after standard of care almost 100 % of the time. There
has been great interest in immunotherapy because it has shown recent success against many types of cancers,
but recent randomized clinical trials in GBM using immune checkpoint inhibitors, peptide vaccines, or dendritic
cell therapies have not been successful. A major reason for the lack of immunotherapy success is likely due to
the highly immunosuppressive microenvironment of GBMs which leads this tumor to be immunologically “cold”.
We are utilizing an oncolytic HSV1 (oHSV) for its dual properties of direct GBM replicative cytotoxicity and of
potent in situ immunostimulation in a phase 1 clinical trial in recurrent GBM. As we begin to analyze data from
this trial, questions arise related to the dose of oHSV and to commonly used concomitant treatments, such as
steroids or bevacizumab. Answers to these questions will help in design of the next steps in clinical trials of this
oHSV. To answer these questions, we have developed pilot data in mouse models of GBM to show how changes
in the immune cell TME affect GBM progression or regression when treated with oHSV. Specifically, our studies
appear to show that anti-GBM responses from oHSV therapy are characterized by an expansion of activated
TILs against a model tumor antigen, whereas GBM progression is characterized by a lack of this expansion.
We thus hypothesize that observed oHSV-mediated anti-GBM responses depend on TIL expansion
against tumor antigen and that factors such as oHSV dose and other concomitant treatments such as
steroids and bevacizumab modulate this. We plan to test these hypotheses by evaluating the kinetics of
expansion of TILs against a model GBM antigen (aim 1) and by determining if standard of care
treatments, such as dexamethasone and/or bevacizumab change TIL expansion against a model GBM
antigen (aim 2). The overall impact of these aims if successful would thus allow us to understand why some
GBM patients appear to respond to oHSV therapy and improve our ability to increase the percentage of
responders.

## Key facts

- **NIH application ID:** 10017354
- **Project number:** 5R01NS110942-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** E. Antonio Chiocca
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,647
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017354

## Citation

> US National Institutes of Health, RePORTER application 10017354, Oncolytic virus therapeutic responses occur from changes in the glioblastoma immune microenvironment (5R01NS110942-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10017354. Licensed CC0.

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