Work

CAR-engineered microglia harness phagocytosis to target brain tumor in organoid models

Year: 2026

Type: article

Abstract: Glioblastoma (GBM) is among the most aggressive and lethal brain tumors, and standard treatment offers only modest survival benefits. Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of hematologic cancers, but its efficacy in GBM remains limited. Here we develop a CAR-engineered microglia (CAR-MG) platform and an organoid-based framework to test whether programmable microglial phagocytosis can be directed against GBM. We isolate microglia (MG) from human cortical organoids and engineer them to express a CAR targeting EGFRvIII, a recurrent tumor-specific EGFR deletion variant in GBM. In a 2D co-culture, CAR-MG selectively eliminates GBM cells through phagocytosis. In a 3D GBM-cortical organoid model, CAR-MG infiltrates tumor sites and depletes GBM cells over extended culture. Single-cell RNA sequencing (scRNA-seq) shows elevated phagocytic pathways in CAR-MG and detects internalized tumor-derived transcripts, which resolve phagocytosis-resistance programs. These results support CAR-MG as a myeloid CAR modality for human brain organoid models.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.118091