Chimeric Antigen Receptor-Macrophage Extracellular Vesicles Reprogram Immune Microenvironment for Cancer Therapy.

In an in vivo liver cancer model, CAR-MEVs administration proved safer than CAR-Ms therapy, reducing tumor burden and prolonging overall survival. In a humanized mouse model, CAR-MEVs further demonstrated the ability to induce a pro-inflammatory tumor microenvironment and enhance anti-tumor T cell activity. Mechanistically, CAR-MEVs target tumor cells, inducing immunogenic cell death (ICD) and subsequently leading to neutrophil infiltration in tumor tissues.

We demonstrated that the anti-tumor effects of CAR-MEVs depend on neutrophils and are partially reliant on inducible nitric oxide synthase (iNOS). This study supports the potential of macrophage extracellular vesicles as a novel therapeutic approach for solid tumors.