# Towards a preventive cancer vaccine for children with constitutional mismatch repair deficiency

> **NIH NIH UG1** · PUBLIC HEALTH INSTITUTE · 2022 · $1,500,000

## Abstract

In children, DNA replication repair deficiency (RRD), caused by mutations in the mismatch repair
of DNA polymerase genes, is an important cancer mechanism. RRD drives a deadly group of
cancers universally characterized by hypermutation, microsatellite instable (MSI) in/dels and
resistance to chemoradiation. Children with germline/constitutional mismatch repair deficiency
(CMMRD) have the highest burden of cancers in humans and rarely reach adulthood. The
exceptionally high number of mutations creates highly immunogenic peptides never expressed in
normal cells called neoantigens. Clinical evidence for the importance of CD8+ T cell activation in
endogenous neoantigen immune surveillance is demonstrated by immune checkpoint inhibitor
(ICI) immunotherapy efficacy. While the success of ICI has led to speculation that they may also
be helpful for primary cancer prevention, ICI also has significant rates of severe adverse events,
including autoimmunity-related lung, hepatic, skin, neuro, colon, endocrine, and lymphoma
toxicities, some of which are fatal. These problems have led to new interest in cancer
immunoprevention vaccines, which have milder and fewer adverse events, to boost cancer
neoantigen immune surveillance. Recently, lipid nanoparticle RNA (LNP-RNA) vaccines against
COVID-19 demonstrated convincingly that LNP-RNA vaccination is faster, more flexible, cheaper
and more immunogenic than any previous vaccine technology. Our overall goal is to leverage
paradigm-shifting advances in molecular diagnosis of CMMRD children as an identifiable high-
risk patient group, a mechanistic understanding of CMMRD derived RRD tumor mutation
architecture, powerful advances in tumor genomics and recent advances in vaccine technology
to pre-clinically discover, formulate, and validate novel LNP RNA vaccines for effective and safe
CMMRD pediatric immunoprevention.

## Key facts

- **NIH application ID:** 10672675
- **Project number:** 3UG1CA189955-09S1
- **Recipient organization:** PUBLIC HEALTH INSTITUTE
- **Principal Investigator:** BRAD H POLLOCK
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,500,000
- **Award type:** 3
- **Project period:** 2014-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10672675

## Citation

> US National Institutes of Health, RePORTER application 10672675, Towards a preventive cancer vaccine for children with constitutional mismatch repair deficiency (3UG1CA189955-09S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10672675. Licensed CC0.

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