May 10, 2026 —
University of Colorado Anschutz Cancer Center researcher Siddhartha Mitra, PhD, has received a three-year grant from the Matthew “Iron Matt” Larson Foundation for Pediatric Brain Tumors to develop CAR macrophage, or CAR M, therapies for diffuse midline gliomas, a highly aggressive pediatric brain cancer with limited treatment options.
CAR M therapy builds on the concept of CAR T-cell therapy, but instead of engineering T cells to recognize cancer targets, it modifies macrophages—immune cells naturally capable of entering tissues, engulfing debris, and attacking abnormal cells. While CAR T-cell therapy has transformed treatment for some blood cancers, its success in solid tumors has been more limited because solid tumor microenvironments can block T-cell infiltration and function. Macrophages may offer a different strategy because they are naturally able to enter solid tumors.
Diffuse midline gliomas are among the most difficult pediatric brain tumors to treat. Because they arise in critical regions of the brain, surgery is often not feasible, and radiation is typically used mainly for temporary symptom relief rather than cure. This creates a major need for new therapies that can penetrate the tumor microenvironment and generate a durable anti-tumor response.
Mitra and collaborators at the CU Anschutz Cancer Center plan to engineer CAR macrophages that can directly attack glioma cells. The team also aims to design the macrophages to secrete cytokines, signaling proteins that may reshape the tumor microenvironment and make it more favorable for T-cell activity. This dual strategy could allow engineered macrophages to both debulk tumor cells and help trigger a longer-term immune response.
The approach reflects growing interest in next-generation cell therapies for solid tumors, where overcoming immune suppression, tumor access, and durable response remain major challenges. If successful, CAR M therapy could provide a new therapeutic direction for pediatric brain tumors that are currently considered among the most difficult cancers to treat.
Mitra, who also has NIH funding to develop CAR macrophage therapies for adult brain cancer, hopes the pediatric program will move toward clinical trial readiness by the end of the three-year grant period. While the work remains preclinical, it represents an important effort to expand cell therapy beyond CAR T cells and into immune cell types better suited for solid tumor biology.
