# A phase I study of RNA-lipid particle vaccines for newly-diagnosed glioblastoma, IND19304 08/21/2020

> **NIH FDA R01** · UNIVERSITY OF FLORIDA · 2024 · $617,119

## Abstract

Project Summary: Despite standard of care with maximal surgical resection, external beam radiotherapy, and
chemotherapy, patients with glioblastoma (GBM) live little more than 18 months after diagnosis; these outcomes
necessitate development of new targeted therapies. To address this gap, our group developed a novel vaccine
formulation that can unlock anti-tumor immunity within hours. By layering tumor mRNA into a multi-lamellar
nano-lipid formulation (for systemic administration), we can make tumor antigens appear like a systemic viral
infection. Our multi-lamellar design delivers increased antigenic load (per particle) triggering potent innate
activation which then facilitates adaptive effector responses. RNA-lipid nanoparticles (RNA-LPs) activate
systemic/intratumoral dendritic cells (DCs), upregulate critical innate gene signatures in the glioma
microenvironment, and induce glioma-specific T cell immunity. In murine tumor models resistant to immune
checkpoint inhibitors, RNA-LPs induce robust anti-tumor efficacy with long-term survivor benefits. We have
previously demonstrated safety of RNA-LPs in acute/chronic murine GLP toxicity studies and launched a large
animal canine glioma trial (IACUC#201609430). Our canine trial demonstrated that RNA-LP administration is
feasible, safe and immunologically active with improvement in overall survival in pet dogs with terminal gliomas
(compared with historical controls). We have since received FDA-IND approval (BB-IND#19304, Sayour) for first-
in-human studies (NCT04573140) in patients with GBM. The purpose of this study is to assess the safety,
maximum tolerated dose (MTD), and immunogenicity of RNA-LPs vaccines in newly-diagnosed adult GBM
patients. We hypothesize that RNA-LPs will mediate systemic immune reprogramming of GBM unlocking
immunotherapeutic activity. Our SPECIFIC AIMS are:
1. Conduct phase I study evaluating safety, MTD and immunogenicity of RNA-LPs against GBM.
 a. Characterize systemic immune response in patients prior to receiving RNA-LPs and effect
 change following vaccination.
 i. Identify immunologic phenotype of myeloid and lymphocyte subsets (naïve, effector, memory,
 regulatory) and NK cells in patients with GBM at diagnosis and throughout therapy.
 ii. Elucidate changes in cytokine profile and pathogen-recognition receptor (PRR) activation
 status in patients with GBM during/after RNA-LP vaccines.
 iii. Identify potential tumor specific antigens as vaccine candidates through whole exome
 sequencing, RNA-seq, and neoantigen prediction analysis.
 b. Establish memory recall T cell immunity in vaccinated patients
 c. Determine if magnitude and persistence of anti-tumor innate and adaptive immunity correlates
 with clinical outcome.

## Key facts

- **NIH application ID:** 10687969
- **Project number:** 5R01FD007268-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Elias Sayour
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2024
- **Award amount:** $617,119
- **Award type:** 5
- **Project period:** 2022-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687969

## Citation

> US National Institutes of Health, RePORTER application 10687969, A phase I study of RNA-lipid particle vaccines for newly-diagnosed glioblastoma, IND19304 08/21/2020 (5R01FD007268-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10687969. Licensed CC0.

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