Abstract
Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary cancer treatment, but it has severe side effects. Extracellular vesicles (EVs), nanovesicles released by CAR T cells, known as CAR T-cell-derived EVs (CAR-EVs), are a potential alternative owing to their role in intercellular communication. This review comprehensively explores the clinical potential of CAR-EVs for cancer therapy, starting with their biogenesis and cargo, which include unique therapeutic molecules. It reviews the mechanisms underlying CAR-EV-mediated anticancer effects and presents preclinical evidence demonstrating efficacy across various cancers, including hematological malignancies and solid tumors. The review further discusses preclinical data and advantages over existing CAR T-cell therapies, emphasizing the need for future clinical studies to assess the safety and efficacy of CAR-EVs in cancer patients. This review also summarizes preliminary findings and challenges, proposing strategies to improve EV targeting and cargo delivery. Additionally, this review highlights unexplored aspects of EV biology in the context of CAR T-cell therapies. In conclusion, CAR-EVs offer a viable option for cancer therapy, with potential advantages over conventional CAR T-cell therapies. However, future research is needed to optimize manufacturing, distribution, and clinical application for achieve maximum therapeutic efficacy and favorable patient outcomes.