# Development of Chimeric Antigen Receptor Phagocytes Against Glioblastoma

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $447,831

## Abstract

Project Abstract: Pediatric HGGs comprise glioblastoma [glioblastoma multiforme (GBM)],
anaplastic astrocytoma, and diffuse intrinsic pontine glioma (DIPG) and collectively are the most
common malignant brain tumors in children. Patients with HGGs have a very dismal prognosis,
with <5% 5-year survival for GBM patients and a median survival of <1 year for patients with
DIPG, pointing to an urgent need for alternative therapeutic approaches. Chimeric antigen
receptors (CARs) are engineered cell surface molecules that combine the specificity of
antibodies with the downstream signaling of effector cells such as T cells. The expression of
CARs on T cells has shown enormous promise by effectively treating malignancies by directly
killing them. However, CAR-T cell therapy is often hampered by the inability of T cells to
penetrate solid tumors and the inhibitory tumor microenvironment (TME). Recently there has
been great interest in developing CAR-macrophages against solid tumors to improve phagocytic
activity and antigen presentation of macrophages against tumors. Here we hypothesize that this
distinctive proficiency of macrophages and microglia to infiltrate malignant brain tumors provides
a unique opportunity to exploit their phagocytic properties by engineering the activation of these
professional phagocytes using exogenous expression of Chimeric Antigen Receptor (CARs)
targeted towards a brain tumor-specific antigen. In Aim 1 we will engineer the most effective
CAR-expressing phagocyte for efficient targeting of pHGG and demonstrate the superior
efficacy of B7H3 CAR phagocyte therapy in combination with blockage of phagocytosis
checkpoint (anti-CD47) immunotherapy in humanized xenograft models of pHGG. In Aim 2 we
will Identify the most efficient cell type that can function as a CAR-expressing phagocyte that
can most efficiently traffic to the brain and target pHGG tumors in combination with blockage of
phagocytosis checkpoint (anti-CD47) immunotherapy and finally in Aim 3 we will study the in
vivo biology of CAR-macrophages and its effect on the TME in syngeneic mouse models of
high-grade pediatric glioma.

## Key facts

- **NIH application ID:** 10937869
- **Project number:** 1R01CA291887-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Siddhartha S. Mitra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $447,831
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937869

## Citation

> US National Institutes of Health, RePORTER application 10937869, Development of Chimeric Antigen Receptor Phagocytes Against Glioblastoma (1R01CA291887-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10937869. Licensed CC0.

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