# Personalized neoantigen vaccines using nucleoside-modified mRNA-lipid nanoparticles

> **NIH NIH U01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $178,000

## Abstract

PROJECT SUMMARY: U01 CA217959 Supplement Application
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-
24-029. The parent Multiple Principal Investigator (MPI) Project proposal for the Pediatric Immunotherapy
Network is focused on high-risk neuroblastoma, a diverse and enigmatic malignancy arising from the developing
sympathetic nervous system that remains lethal in 50% of patients despite intensive multi-modal therapy. There
is an urgent unmet need for developing novel therapeutic interventions to decrease the incidence of relapse,
increase overall survival, and reduce devastating toxicities associated with standard therapy. The primary goal
of this Project is to achieve improved outcomes for patients with high-risk neuroblastoma through the
development of a personalized vaccination strategy targeting individualized neoantigens. The central hypothesis
is that high-risk neuroblastomas, despite a low tumor mutation burden (TMB), harbor a sufficient number of
neoepitopes through canonical and non-canonical mutations to identify, predict, and validate optimal neoantigen
peptides to engineer effective multivalent personalized neuroblastoma vaccines. The motivation for the proposed
research is the urgent need to improve survival and to decrease treatment-related morbidities for patients with
high-risk neuroblastoma. Indeed, the majority of high-risk neuroblastoma patients achieve a remission with
standard therapy, and here we seek to engage the adaptive immune system to eradicate residual disease and
prevent relapse. We will test our hypothesis through the two Specific Aims: 1) define the neoantigen landscape
of high-risk neuroblastoma patient and genetically engineered mouse model (GEMM) tumors; 2) develop and
test a readily translatable personalized vaccination strategy.
In this new supplemental application, we take advantage of the expertise of the expertise of Dr. Drew Weissman
and his University of Pennsylvania RNA Innovation Institute to develop mRNA-based lipid nanoparticle
personalized neuroblastoma vaccines to be tested in parallel with the multivalent peptide vaccines we are
pursuing in the parent award. This will extend the potential impact of this U01 Project by providing an alternative
path to clinical translation that may have advantages that we will define in this supplemental sub-Project.

## Key facts

- **NIH application ID:** 11074873
- **Project number:** 3U01CA281881-02S1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** JOHN M MARIS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $178,000
- **Award type:** 3
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11074873

## Citation

> US National Institutes of Health, RePORTER application 11074873, Personalized neoantigen vaccines using nucleoside-modified mRNA-lipid nanoparticles (3U01CA281881-02S1). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/11074873. Licensed CC0.

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