# Developmentally regulated antigens for immunologic targeting of pediatric brain tumors

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2023 · $419,375

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Brain tumors are the number one cause of cancer related deaths in children. Medulloblastoma (MB) is
the most common malignant pediatric brain tumor, while brainstem gliomas (BSG) are the most lethal. Though
numerous preclinical and clinical studies have demonstrated potential therapeutic benefits for immunotherapy in
solid tumors, malignant brain tumors remain universally lethal. In response, our group has pioneered an adoptive
cellular therapy platform that relies on the transfer of tumor-reactive T cells and our publications demonstrate
that this platform is efficacious against orthotopic high grade gliomas (KR158B, GL261), Group 3 MB (NSC),
Sonic hedgehog MB (Ptc), and brainstem glioma (K2). In this proposal, our objective is to increase the specificity
and efficacy of adoptive cellular therapy by employing a more targeted approach against embryonal tumors,
specifically MB and brainstem gliomas (BSG).
 Recent elegant studies have identified links between ontogeny and oncology, describing that
dysregulation in neural developmental processes lead to childhood CNS tumors, suggesting these cancers arise
as a consequence of abnormal developmental processes. This provides great opportunity to leverage developing
neural tissue as a source of antigens against MB and BSG. We refer to this genomic intersection between
developing tissue and tumors as developmental antigens (DevAg). In this proposal we will identify the DevAgs
in both MB and BSG and leverage them for immunological targeting of these tumors. Targeting these
developmentally regulated antigens not only negates the requirement for primary tumor resection but also limits
potential cross-reactivity with normal gene products. Importantly, this indicates that developing cerebellum do
share immunogenic antigens with different subtypes of MB and that multiple subtypes of MB can be targeted by
developmental antigens. To our knowledge, our studies are the first to 1. Utilize developing brain antigens to
target syngeneic MB and BSG murine models and 2. demonstrate antitumor efficacy using a novel method of
targeted enrichment to select for specific antigens. This approach has profound implications in safely and
effectively targeting MB and BSG.

## Key facts

- **NIH application ID:** 10751884
- **Project number:** 1R21NS134145-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Catherine T Flores
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $419,375
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751884

## Citation

> US National Institutes of Health, RePORTER application 10751884, Developmentally regulated antigens for immunologic targeting of pediatric brain tumors (1R21NS134145-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10751884. Licensed CC0.

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