# Engineering RNA-nanoparticles to enhance dendritic cell mediated treatment of glioblastoma

> **NIH NIH F30** · UNIVERSITY OF FLORIDA · 2020 · $50,520

## Abstract

Abstract
Despite aggressive chemotherapy, surgical resection, and radiation therapy, glioblastoma (GBM) remains
almost universally fatal. A recent randomized, control trial demonstrated RNA-loaded dendritic cell (DC)
vaccines significantly prolong overall and progression free survival in patients with primary GBM. Moreover,
this trial also demonstrated that dendritic cell migration to lymph nodes could be used a clinically meaningful
predictor of patient response to treatment. This technique provides researchers a surrogate endpoint to
develop enhanced dendritic cell vaccine protocols and could provide clinicians with a powerful tool to predict
patient response to treatment just 48 hours after vaccination. However, the high regulatory requirements
associated with standard methods of tracking cell migration limit future application of this technique.
This project is designed to evaluate use of theranostic RNA-loaded nanoparticles (RNA-NPs) to enhance and
track DC migration to LNs. Preliminary evidence indicates that RNA-NPs 1) stimulate potent DC activation 2)
enhance DC migration to LNs, and 3) can be loaded with sufficient levels of iron oxide to be tracked with MRI.
This study will test the hypothesis that RNA-NPs can be used to enhance DC migration to LNs, predict vaccine
efficacy with MRI, and improve antitumor immune responses. These goals will be assessed with the following
Specific Aims:
Aim 1: Determine effects of RNA-NP loading on dendritic cell activation and migration to LNs
Unique benefits of RNA-NP loading on DC activation will be assessed with genomic analysis of intracellular
signaling pathways. Functional consequences of RNA-NP loading will be determined in a murine model of our
vaccine protocol.
Aim 2: Determine predictive utility of MRI-detected dendritic cell migration
The sensitivity of MRI based detection of RNA-NP loaded DCs will be determined by correlating changes in MRI
intensity to absolute counts of RNA-NP-loaded DsRed+ DCs in lymph nodes. The predictive value of MRI-
detected DC migration will then be assessed in a murine glioma model.
Aim 3: Evaluate efficacy of RNA-NP loaded dendritic cells in a murine model of GBM
Mice will be vaccinated with RNA-NP-loaded DCs. Antigen specific T cell activation will be assessed with a T
cell killing assay. Survival benefit over other DC preparation methods will be assessed in an aggressive
temozolomide and radiation resistant murine model of high grade glioma.
Significance This project promises to produce a powerful tool to enhance and predict long term survival in
patients with GBM. The combination of a readily accessible imaging component with a robustly stimulatory
nanoparticle formulation would allow streamlined manufacturing of a low cost, theranostic nanoparticle that
would provide clinicians an unprecedented advantage in patient management.

## Key facts

- **NIH application ID:** 9918273
- **Project number:** 5F30CA228280-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Adam Grippin
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-05-16 → 2021-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918273

## Citation

> US National Institutes of Health, RePORTER application 9918273, Engineering RNA-nanoparticles to enhance dendritic cell mediated treatment of glioblastoma (5F30CA228280-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9918273. Licensed CC0.

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