# Investigating mechanisms of peptide alarm therapy

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2022 · $42,049

## Abstract

Project Summary/Abstract:
 Cancer Immunotherapies shift tumor microenvironments from immunosuppressive to immune-activated.
Despite some success with potentially-curative treatments, many patients do not exhibit durable responses,
necessitating novel approaches to enhance tumor immunotherapy. “Peptide alarm therapy” is a novel cancer
immunotherapy that repurposes antiviral memory CD8+ T cells within tumors to drive antitumor immunity.
After a primary infection, pathogen-specific CD8+ T cells establish a surveillance program that positions T cells
throughout the entire body. In particular, resident-memory CD8+ T cells (Trm) permanently reside in all tissues
after primary antigen exposure. In addition to normal tissue, antiviral Trm populate solid tumors.
Notably, in contrast to tumor-specific T cells, intratumoral antiviral Trm are not exhausted and demonstrate
potent immune activation upon engagement with their cognate antigen. Our group showed that Trm
reactivation in both normal tissues and tumors leads to inflammatory processes, including the
production of immune-stimulatory cytokines and chemokines (e.g. IFNg, TNFa, CCL9), and the local
recruitment of effector molecules (e.g. antibodies) and immune cells (e.g. circulating memory T cells, NK cells).
The intratumoral injection of peptide, and this subsequent reactivation of antiviral Trm, induces tumor
growth suppression and exhibits synergy with immune checkpoint blockade, specifically aPD-L1. The
mechanisms driving this antitumor immune response remain uncharacterized. In this proposal, I will employ
well-established murine models of T cell memory and melanoma to explore the mechanisms that drive the
antitumor response of peptide alarm therapy. Aim 1 will determine whether viral peptide presentation by
cancer cells is necessary for treatment efficacy, potentially demonstrating that, through peptide alarm therapy,
antiviral Trm can directly kill cancer cells in a peptide:MHCI-dependent mechanism. Aim 2 will measure and
monitor tumor-specific T cells and NK cells, determining their respective role in controlling tumor growth in the
context of this cancer therapy. Not only will this work add value to preclinical data for a promising new
immunotherapy, but it will also relay information about how Trm can be manipulated for therapeutic use.
 This proposal will be completed at the University of Minnesota in the laboratory of David Masopust, Ph.D.,
a world-leader in the study of memory T cell function and immunosurveillance. Along with mentorship from Dr.
Masopust, the collaborative training environment at the University’s Center for Immunology and the integrated
training provided by the Medical Scientist Training Program (dual-degree MD/PhD program) will serve as an
ideal location for me to develop as a predoctoral trainee. My long-term career goal is to become an
academic physician scientist who drives translational research as an internal medicine clinician and
specialist in immunology.

## Key facts

- **NIH application ID:** 10425397
- **Project number:** 5F30CA253992-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Noah Veis Gavil
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $42,049
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425397

## Citation

> US National Institutes of Health, RePORTER application 10425397, Investigating mechanisms of peptide alarm therapy (5F30CA253992-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10425397. Licensed CC0.

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