Review Article: The Evolution and Future of Immunotherapy: The Promise of CAR T Cell-Derived Extracellular Vesicles.

CAR T cell therapy, pioneered by Prof. Zelig Eshhar, has transformed hematologic malignancies but faces significant barriers in solid tumors, including poor infiltration, toxicity, and cytokine release syndrome. This perspective explores CAR T cell-derived extracellular vesicles (CAR T EVs) as an emerging platform that extends Eshhar's vision by delivering CAR-mediated cytotoxicity with enhanced tumor penetration, physiological barrier, and reduced immunogenicity. EVs carry functional CARs as immunomodulatory cargo, enabling precise antigen targeting without cellular proliferation risks. Key advantages and challenges are reviewed. Building on Eshhar's foundational work, CAR T EVs represent a nanotechnology-immunotherapy alternative.