Dendritic Cell-Derived Extracellular Vesicles as Therapeutic Cancer Vaccines: Mechanisms and Optimization Strategies

Extracellular vesicles (EVs) are ubiquitously secreted nanoparticles that modulate the activities of recipient cells either through the transfer of bioactive cargo or by surface receptor-mediated signalling. EVs derived from dendritic cells are increasingly recognised as promising platforms for therapeutic cancer vaccines, owing to their immunostimulatory cargo, their capacity to transfer preformed peptide-major histocompatibility complexes to antigen-presenting cells, and their ability, in some cases, to directly activate cognate T cells. Despite encouraging preclinical results, EV-based cancer vaccines have demonstrated limited clinical efficacy, constrained by suboptimal immunogenicity, poor lymphoid targeting, and suppression within the tumour microenvironment. Several strategies-including prioritising tumour-specific neoantigens, co-administering adjuvants and immunotherapies, optimising EV production and delivery protocols, and engineering EVs with tailored characteristics-aim to overcome these limitations and improve clinical outcomes.