Human chimeric antigen receptor macrophages for cancer immunotherapy.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging^1-4. Given the unique effector functions of macrophages and their capacity to penetrate tumors⁵, we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype. CAR macrophages (CAR-Ms) demonstrated antigen-specific phagocytosis and tumor clearance in vitro. In two solid tumor xenograft mouse models, a single infusion of human CAR-Ms decreased tumor burden and prolonged overall survival. Characte

SUBMITTER: Klichinsky M 

PROVIDER: S-EPMC7883632 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature