B7-H3 CAR T-cell therapy + DNMT inhibitor

B7-H3 CAR T-cell therapy + DNMT inhibitor is an experimental combination strategy designed to treat pediatric brain tumors, such as glioma and medulloblastoma. This approach utilizes Chimeric Antigen Receptor (CAR) T-cells engineered to target B7-H3 (CD276), a protein frequently overexpressed in solid tumors. To overcome the challenges of T-cell exhaustion and poor persistence in the tumor microenvironment, DNA methyltransferase inhibitors (DNMTis)—including azacytidine, zebularine, and GSK3685032—are added during the GMP-compatible manufacturing process. This "epigenetic priming" modulates the T-cell's DNA methylation patterns, leading to enhanced expansion, increased cytokine production, and a shift toward a central memory phenotype. Preclinical studies conducted by Children’s National Hospital and George Washington University have demonstrated that DNMTi-primed CAR T-cells exhibit superior persistence and the ability to clear tumors upon rechallenge compared to standard CAR T-cells.

Other names

B7-H3 CAR T-cell therapy + azacytidineB7-H3 CAR T-cell therapy + zebularineB7-H3 CAR T-cell therapy + GSK3685032