# Harnessing the Immunologic Capacity of RNA-nanoparticle Vaccines Targeting Glioblastoma

> **NIH NIH K08** · UNIVERSITY OF FLORIDA · 2020 · $158,188

## Abstract

Abstract:
I am now in my first faculty position as an Assistant Professor of Neurosurgery and Pediatrics at the University
of Florida. I completed a T32 NIH fellowship at Duke University in Cancer Biology and Developmental
Therapeutics before accepting a junior faculty position at the University of Florida where I moved with my
mentor, Dr. Duane Mitchell. Dr. Mitchell and I have selected an advisory committee to ensure accrual of my
intellectual and professional growth. The non-overlapping expertise of our advisory committee will be an
avenue for me to develop new knowledge in tumor immunology, molecular biology, nanotechnology and
translational oncology. This proposal will leverage much of this experience as it outlines a career development
plan for me to become an independent investigator exploring novel RNA-nanoparticle vaccines that can re-
direct the immune system against malignant brain tumors.
Background: Glioblastoma (GBM) remains almost uniformly lethal with a median survival of less than 15
months thus necessitating the development of more efficacious and targeted therapeutics. While we have
shown in a randomized/blinded trial that RNA-pulsed dendritic cell (DC) vaccines elicit significant survival
benefits in GBM patients, these therapies remain encumbered by cost and complexity. Alternatively, RNA-
nanoparticles (RNA-NPs) can deliver total tumor RNA (TTRNA), extracted and amplified from as few as 500
biopsied tumor cells, to endogenous antigen presenting cells (APCs) inducing potent, nontoxic anti-tumor
immunity. Since these nanoliposomes have been used with limited toxicity in clinical-grade medicine, are
stable for several hours in solution, protect nucleic acids from degradation, and can be engineered to modulate
immune responses, we have explored the use of TTRNA-loaded NPs as an attractive, “off-the-shelf”
therapeutic platform to re-direct host-immunity against intracranial tumors. While we have demonstrated that
intravenous delivery of RNA-NPs mediate antigen specific T cell responses against intracranial malignancies
comparable to DC vaccines, these formulations were shown to induce differential phenotypes on APCs in the
spleen and liver.
Hypothesis: RNA-NPs transfect distinct APCs in the spleen and liver inducing differential immune responses
that can be modulated in favor of enhanced effector functions.
Specific Aims:
1) Determine critical APC subsets and evaluate their role in RNA-NP mediated immune responses.
2) Identify regulatory pathways involved in RNA-NP mediated immunity and investigate capacity to target
these pathways through incorporation of immunomodulatory RNAs into vaccine formulations.
3) Evaluate the safety and efficacy of the most promising RNA-NP formulation in a malignant murine glioma
model.
Research Design: We propose to identify critical APCs involved in RNA-NP mediated immunity, target
regulatory pathways identified after vaccination, and evaluate the safety and efficacy of RNA-NPs in an
invasive precli...

## Key facts

- **NIH application ID:** 9996507
- **Project number:** 5K08CA199224-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Elias Sayour
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,188
- **Award type:** 5
- **Project period:** 2016-09-13 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996507

## Citation

> US National Institutes of Health, RePORTER application 9996507, Harnessing the Immunologic Capacity of RNA-nanoparticle Vaccines Targeting Glioblastoma (5K08CA199224-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996507. Licensed CC0.

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