Chimeric antigen receptor-microglia targeting glioblastoma within cortical organoid

Although chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, its clinical benefits in GBM have been limited. To address this challenge, we developed a novel therapeutic strategy employing CAR-engineered microglia (MG).

Utilizing human cortical organoids incorporating microglia (mhCOs), we isolated endogenous MG and genetically modified them to express a CAR targeting EGFRvIII, a predominant de novo mutation frequently observed in GBM. To further characterize the engineered microglia and elucidate their transcriptional landscape, four distinct mhCO-derived samples were analyzed via single-cell RNA sequencing (scRNAseq). This dataset provides comprehensive insights into the cellular heterogeneity, CAR expression profiles, and potential immunomodulatory functions of the modified microglia, thereby underpinning their therapeutic promise in targeting GBM.