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

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2021 · $262,400

## Abstract

Oncolytic viruses (OV) are a promising class of cancer therapeutics that work by preferentially infecting and
killing tumor cells. Many OVs are viruses which individuals have pre-existing immunity to, 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:** 10271750
- **Project number:** 2P20GM113132-06
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Pamela Rosato
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $262,400
- **Award type:** 2
- **Project period:** 2016-05-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271750

## Citation

> US National Institutes of Health, RePORTER application 10271750, Impact of pre-existing T cell memory on oncolytic virus therapy (2P20GM113132-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10271750. Licensed CC0.

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