Extracellular Vesicles as Immunotherapeutic Mediators in Gastrointestinal Cancers and Diseases: From Mechanisms to Clinical Translation

Le résumé fourni par la source

Immunotherapy has transformed cancer treatment, yet its efficacy in gastrointestinal (GI) cancers and inflammatory diseases remains limited, underscoring the need for more effective immunomodulatory strategies. Multiple biomaterial-based delivery platforms, including liposomes, polymeric nanoparticles, viral vectors, and inorganic nanocarriers, have been employed to enhance immune regulation and therapeutic transport. However, their clinical translation is hindered by intrinsic limitations such as immunogenicity, variable biocompatibility, nonspecific tissue distribution, payload instability, and challenges in scalable and reproducible manufacturing. These constraints highlight the need for safer and more clinically adaptable delivery systems. Extracellular vesicles (EVs), as naturally derived nanoscale carriers, have emerged as promising therapeutic tools due to their unique advantages, such as biocompatibility, low immunogenicity, precise targeting, and multifunctional molecular delivery. This review synthesizes recent advances in EV-based immunotherapeutic strategies for GI cancers and diseases, emphasizing approaches relevant to clinical pharmacology. Key innovations include EV vaccines, modulation of the immune microenvironment using cell source-specific EVs, and engineered EVs for the targeted delivery of cytokines, nucleic acids, or immune checkpoint inhibitors. Emerging applications involving EV-mediated transport of CAR constructs, oncolytic agents, and gene-editing tools further broaden their therapeutic potential. In conclusion, EV-based therapies offer transformative approaches through multimodal immune modulation and precision drug delivery to GI diseases. However, standardization, large-scale manufacturing, targeted delivery, and addressing tumor heterogeneity with personalized EV engineering will be crucial for clinical success in GI diseases. Overcoming these barriers will accelerate EV integration into next-generation immunotherapy and precision oncology.

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