# Impact of pre-existing T cell memory on oncolytic virus therapy

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2020 · $267,764

## Abstract

Oncolytic viruses (OV) are a promising class of cancer therapeutics that work by preferentially infecting and 
killing tumor cells. Many OVs are viruses to which individuals have pre-existing immunity, through vaccination 
or natural infection (e.g. HSV-1, measles, and vaccinia virus), yet the impact of this immunity on therapeutic 
efficacy and patient outcome is unclear. Recent findings have revealed that virus-specific memory T cells 
populate tumors, often to high frequency. Because of their location within the tumor, it is likely these memory 
T cells will encounter viral antigen during OV therapy. In light of this, there is a critical need to understand 
the impact of oncolytic virus-specific T cells on OV therapy. The objectives in this proposal are to (i) determine 
the frequencies of T cells specific for common OV-based viruses present in tumors and (ii) determine the 
extent to which these T cells strengthen OV therapy. This proposal builds on the findings that virus-specific 
T cells are abundant in a wide range of mouse and human tumors and can elicit potent inflammatory 
responses upon re-encountering their specific viral antigen, resulting in tumor clearance in mice. Given this, 
this proposal will test the central hypothesis that pre-existing OV-specific T cell memory will enhance oncolytic 
virus therapy by promoting immune activation and tumor cell killing. This hypothesis will be tested by 
integrating techniques examining transcriptional and cellular changes in both mouse and human tumor 
tissue. Aim 1 will utilize mouse models of melanoma to determine the impact of oncolytic virus-specific T cells 
on the efficacy of OV therapy and assess how different treatment schedules may enhance this. Aim 2 will 
examine oncolytic virus-specific T cells in human melanoma tumors, investigating their frequency and 
function. By defining the response of antiviral T cells to OV therapy, we will provide a strong scientific 
framework whereby new strategies to refine and re-design OV therapies can be developed. Collectively, 
these experiments will advance our understanding of the immune composition of solid tumors and inform the 
field of oncolytic viral therapies. This proposal will provide a foundation for a competitive R01 aimed at 
understanding 1) immune responses during OV therapy in patients, 2) the predictive potential of OV-specific 
T cell abundance on therapeutic outcome, and 3) how OV therapies can be refined or re-designed to improve 
outcome. In all, the studies proposed here will have an impact on clinical patient care and drive the 
development of novel immunotherapies.

## Key facts

- **NIH application ID:** 10226591
- **Project number:** 5P20GM113132-05
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Pamela Rosato
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $267,764
- **Award type:** 5
- **Project period:** 2020-07-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226591

## Citation

> US National Institutes of Health, RePORTER application 10226591, Impact of pre-existing T cell memory on oncolytic virus therapy (5P20GM113132-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10226591. Licensed CC0.

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