Harnessing CAR-Extracellular Vesicles for Next-Generation Cancer Immunotherapy.
Cancer immunotherapy has experienced substantial progress in recent years, particularly with the advancement of chimeric antigen receptor (CAR) technology, which enables immune cells to selectively target tumor-associated antigens. CARs, now in their fifth generation, are engineered by combining monoclonal antibody fragments with signaling and co-stimulatory domains and have been successfully applied to T cell, natural killer (NK) cell, and macrophage-based therapies. Notable clinical successes, such as tisagenlecleucel and lisocabtagene maraleucel underscore the therapeutic potential of CAR-T, CAR-NK and CAR-macrophages (CAR-Ms), which are currently being evaluated in numerous clinical trials. One promising extension of this approach involves the use of extracellular vesicles (EVs) derived from these immune cells. These nano-sized vesicles offer a cell-free platform to deliver diverse anticancer mediators, addressing the complex and dynamic nature of tumor environments. In this review, we examine the therapeutic potential and immunogenic properties of CAR-derived EVs, along with their role in modulating immune responses. Furthermore, we explore their application as targeted delivery vehicles for chemotherapeutic agents, with the goal of enhancing anti-tumor efficacy while minimizing systemic toxicity.
Authors
Chelvaretnam Chelvaretnam, Mom Mom, Palma Henriquez Palma Henriquez, Pham Pham, Fitri Fitri, Bhuiyan Bhuiyan, Shojaee Shojaee, Asari Asari, Rashid Rashid, Hinch Hinch, Khanabdali Khanabdali, Rice Rice
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