Chimeric antigen receptor (CAR) macrophages may represent a promising anti-cancer immune therapy strategy due to their favourable biological properties but in vitro manipulation and targeting to specific organs could be challenging. Here authors use inhalable small extracellular vesicles to deliver the CAR mRNA construct to macrophages in the lung and show that the thus in situ generated CAR macrophages successfully combat lung metastasis and cancer recurrence in a mouse model.