The University of Colorado Cancer Center has received a USD 1.28 million NIH R01 renewal from the National Cancer Institute to develop chimeric antigen receptor (CAR)-engineered phagocytes as a treatment for pediatric high-grade gliomas, a group of brain cancers with historically poor outcomes. The grant, led by principal investigator Siddhartha S. Mitra, funds work through mid-2029 and reflects continued NCI investment in cellular immunotherapy approaches for tumors that have resisted conventional CAR-T strategies.
The project targets glioblastoma, anaplastic astrocytoma and diffuse intrinsic pontine glioma, where five-year survival for glioblastoma remains below 5% and DIPG median survival is under one year. Rather than engineering T cells, Mitra's team is modifying macrophages and microglia—immune cells naturally able to infiltrate brain tumors—to express CARs against the tumor antigen B7-H3. The approach is designed to pair CAR-phagocyte therapy with blockade of CD47, a "don't eat me" signal tumors use to evade immune clearance. The strategy addresses a known limitation of CAR-T therapy in solid tumors: poor T-cell penetration and an immunosuppressive microenvironment. Work spans humanized xenograft and syngeneic mouse models, with aims covering phagocyte engineering, optimal cell trafficking to the brain, and effects on the tumor microenvironment.
The award is a non-competing continuation of an existing R01, indicating the project has cleared its initial funding period and NCI review milestones. It adds to a small but growing set of NIH-backed programs exploring macrophage-based CAR engineering as an alternative to T-cell platforms, particularly for pediatric brain tumors where drug delivery across the blood-brain barrier and immune-cell trafficking remain persistent obstacles. The work remains preclinical, with no stated timeline for clinical translation.
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