Harnessing engineered extracellular vesicles for enhanced therapeutic efficacy: advancements in cancer immunotherapy

Extracellular vesicles (EVs), particularly engineered variants, have emerged as promising tools in cancer immunotherapy due to their inherent ability to modulate immune responses and deliver therapeutic agents with high specificity and minimal toxicity. These nanometer-sized vesicles, which include exosomes (Exos) and other subtypes, naturally participate in intercellular communication and are capable of carrying a diverse range of bioactive molecules, including proteins, lipids, RNAs, and metabolites. Recent advancements in the biogenesis of engineered EVs, such as strategies to modify their surface characteristics and cargo, have significantly expanded their potential as effective vehicles for targeted cancer therapies. Tailoring the contents of EVs, such as incorporating immunomodulatory molecules or gene-editing tools (GETs), has shown promising outcomes in enhancing anti-tumor immunity and overcoming the immunosuppressive tumor microenvironment (TME). Moreover, optimizing delivery mechanisms, through both passive and active targeting strategies, is crucial for improving the clinical efficacy of EV-based therapies. This review provides an overview of recent developments in the engineering of EVs for cancer immunotherapy, focusing on their biogenesis, methods of content customization, and innovations in cargo delivery. Additionally, the review addresses the challenges associated with the clinical translation of EV-based therapies, such as issues related to scalability, safety, and targeted delivery. By offering insights into the current state of the field and identifying key areas for future research, this review aims to advance the application of engineered EVs in cancer treatment. © The Author(s) 2025.