초록 |
Chimeric antigen receptor-T (CAR-T) cell therapy has proven to be effective for hematologic malignancies. However, laborious process of ex vivo cell harvesting from patients and in vitro CAR-cell manufacturing, limit its widespread applications. Moreover, its therapeutic efficacy against solid tumors is hindered due to limited tumor infiltration and inactivation by the immunosuppressive tumor microenvironment. Here, we describe a facile approach for in vivo targeting and programing of macrophages with tumor-recognizing abilities. Injection of mannose-conjugated polymer and CAR-encoding plasmid complexes demonstrated efficient delivery and polarization of tumor-associated M2 to M1 phenotype. Induced CAR-M1 macrophages showed penetration, cancer-directed phagocytosis, anti-tumor activity, and prolonged survival. Altogether, off-the-shelf CAR-M1 macrophage therapy may hold translational potential and provide a convenient, on-demand, and cost-effective treatment against solid tumors. |