# Defining a therapeutic platform for DIPG with mRNA CAR T cells and microglia inhibition

> **NIH NIH K08** · CHILDREN'S HOSP OF PHILADELPHIA · 2022 · $180,211

## Abstract

PROJECT SUMMARY/ABSTRACT
Dr. Jessica Foster's career goal is to become a translational physician-scientist focused on immunotherapy for
pediatric brain tumors. This proposal describes a five-year plan to facilitate her transition to independence
through the acquisition of critical technical skills and scientific training in brain tumor modeling and evaluation
of the tumor microenvironment with single cell RNA sequencing, integrated with comprehensive mentoring
from a diverse team of faculty members. She will conduct the proposed studies under the proven mentorship of
Dr. John Maris, an international leader in translational neuroblastoma research and immunogenomics.
Additionally, her dedicated Advisory Committee is comprised of highly regarded physician-scientists with
diverse expertise in immunotherapy and pediatric brain tumors. Finally, the collaborative research environment
with unparalleled resources at the University of Pennsylvania and the Children's Hospital of Philadelphia
provides an ideal setting to conduct these translational studies.
Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor that remains incurable despite
decades of clinical trials, with a median survival of 11 months. This proposal seeks to use chimeric antigen
receptor (CAR) T cell therapy, a form of immunotherapy, to target DIPG. Recently GD2 was identified as an
immunotherapeutic target for DIPG, and lentiviral GD2-directed CAR T cells were able to successfully treat
murine models of DIPG. However, a significant number of mice treated with CAR T cells died due to
inflammation and herniation, prompting concerns for potential toxicity from this therapy, in particular in the
pons. This proposal is building upon the applicant's experience utilizing mRNA for the creation of CAR T cells
that are transient and can be titrated to effect to avoid toxicity, here using repeated local delivery of GD2-
directed mRNA CAR T cells to effectively treat DIPG while still maintaining safety. Aim 1 will determine the
effect of GD2-directed mRNA CAR T cells on tumor, microenvironment and normal tissue using both
immunocompetent and xenograft models of DIPG. Aim 2 will use single cell RNA sequencing to investigate the
role of microglia in DIPG development and test mRNA CAR T cells in combination with inhibition of microglia.
Dr. Foster's ultimate goal is to create a clinical trial for patients with DIPG using mRNA CAR T cells directed
against GD2, as well as generating a new treatment platform for all pediatric brain tumors. These efforts will
provide an outstanding foundation for her career as a physician-scientist and the development of an
independent translational research program.

## Key facts

- **NIH application ID:** 10485993
- **Project number:** 5K08CA263179-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Jessica B Foster
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $180,211
- **Award type:** 5
- **Project period:** 2021-09-09 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485993

## Citation

> US National Institutes of Health, RePORTER application 10485993, Defining a therapeutic platform for DIPG with mRNA CAR T cells and microglia inhibition (5K08CA263179-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10485993. Licensed CC0.

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