# H3K27M as a Target for RNA-nanoparticles in the Treatment of Diffuse Intrinsic Pontine Glioma

> **NIH NIH R25** · UNIVERSITY OF FLORIDA · 2024 · $75,099

## Abstract

Diffuse Midline Glioma (DMG) is an inoperable pediatric brain tumor with no good treatment options.
Our group has developed a novel treatment modality for this disease and others, using mRNA vaccines
consisting of tumor derived antigens packed into a unique lipid nanoparticle (NP). They can provide near
immediate immune induction against inciting malignancies. RNA-NPs can thus be harnessed as an
effective therapy for patients with DIPG and other refractory malignancies. In addition, DIPG has a
highly conserved H3K27M mutation that serves as an excellent target for these therapies.
Based on the above, we propose exploring the immunogenicity of RNA-NPs targeting the DIPG
H3K27M mutation, as well as the feasibility, safety, and anti-tumor activity of tumor loaded RNA-NP
vaccines in animal models. These RNA NPs have shown survival benefit in our preclinical murine model
of DMG. Among these animals with significant survival benefit, there is development of hydrocephalus,
which is thought to be secondary to increased lesion size secondary to an immunotherapeutic response
during treatment. In our clinical trials investigating RNA NPs as a treatment for canine glioma in adult
dogs, we saw a similar effect in MRI imaging of animals that became long-term survivors. Following
detailed analysis of these lesions in mouse, canine and human patients during RNA-NP therapy, there
appears to be features of both reactive gliosis and traditional pseudoprogression (immune infiltration),
suggesting a new radiographic diagnosis I have named paraprogression. I hypothesize that
paraprogression is a novel radiographic entity characterized by reactive gliosis and increased lesion size
in therapeutic responders. In this study, I aim to visualize paraprogression using advanced MRI
techniques, elucidate the mechanism behind the increase in lesion size, and combat this effect without
compromising our promising survival benefit conferred by RNA NP vaccine in our preclinical DMG
model.

## Key facts

- **NIH application ID:** 10951747
- **Project number:** 3R25NS108939-05S2
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Brian Lim Hoh
- **Activity code:** R25 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $75,099
- **Award type:** 3
- **Project period:** 2019-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951747

## Citation

> US National Institutes of Health, RePORTER application 10951747, H3K27M as a Target for RNA-nanoparticles in the Treatment of Diffuse Intrinsic Pontine Glioma (3R25NS108939-05S2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10951747. Licensed CC0.

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