# Diversity Supplement: Hernandez-Aguirre- Cripe U54

> **NIH NIH U54** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2022 · $172,073

## Abstract

Abstract – Project 3:
Enhancing antigen and cytokine expression to break immune tolerance and improve antitumor
response
Gliomas, like other solid tumors, restrict immune recognition of aberrant cancer cells. Further complicating this,
pediatric cancers also have lower mutation rates than adult tumors making them more difficult to generate an
immunotherapeutic response. This proposal addresses three mechanisms contributing to immune resistance in
pediatric tumors: 1) low mutational loads, 2) myeloid immunosuppressive environment, and 3) MHC
downregulation (immuno-editing). We have developed a multimodal virus based vaccine platform that uses the
virus’s natural ability to recruit immune cells and break immune tolerance to improve immune activity against
the tumor. By encoding tumor associated self-antigens within the viral genome so that they are expressed
during infection our results show that we can convert the antiviral response into an anti-tumor response. The
studies described in our proposal seek to improve our virus-based multi-modal vaccine approach to overcome
immune restriction in one of the most difficult to treat solid tumors, malignant glioma. We propose testing our
hypothesis that: Engineered viral modifications that enhance native and adoptive immune cell activity will
improve durable anti-tumor activity in treatment resistant pediatric gliomas by the following aims.
Aim 1: To improve the immune mediated antitumor response through virus based tumor associated
Fetal Antigen (TAFA) expression. Hypothesis: Viral based TAFA expression enhances T cell activity against
tumor proteins and will extend anti-tumor activity after viral replication ceases.
Aim 2: To promote antigen presentation and a durable anti-tumor immune response. Hypothesis:
Engineering high affinity antigens will enhance their uptake in tumor associated macrophages and improve the
durable anti-tumor response.
Aim 3: To enhance antitumor activity by combining cytotoxic cellular therapies with oncolytic HSVs
that improve immune cell recruitment and activity. Hypothesis: Viruses that enhance cytotoxic cellular
therapy recruitment and activity will improve anti-tumor effect in the immunoedited tumor environment
Impact: If successful, this flexible multimodal viral vaccine platform will harness and direct the immune
stimulatory properties of a next generation oHSV in combination with cellular immune therapies to enhance
their activity against low mutational load immunotherapy-resistant tumors and thus fits well into the aims of the
Pediatric Immunotherapy Drug and Development Network (PI-DDN).

## Key facts

- **NIH application ID:** 10533425
- **Project number:** 3U54CA232561-01A1S5
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** TIMOTHY P CRIPE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $172,073
- **Award type:** 3
- **Project period:** 2019-09-12 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10533425

## Citation

> US National Institutes of Health, RePORTER application 10533425, Diversity Supplement: Hernandez-Aguirre- Cripe U54 (3U54CA232561-01A1S5). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10533425. Licensed CC0.

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