Abstract
Amid the evolving landscape of immunotherapy, the pursuit of safer, more precise, and broadly applicable vaccine platforms has intensified. While conventional technologies-such as lipid nanoparticle-based mRNA systems-achieved unprecedented success in infectious disease prophylaxis, their limitations in safety and durability have prompted the search for alternatives to address more complex immunological challenges, particularly in oncology. Within this context, extracellular vesicle (EV)-based vaccines have emerged as a next-generation platform. These endogenously derived nanoscale vesicles, secreted by nearly all cell types, mirror the immunological identity of their origin and support diverse immune functions. Advances in EV research have enabled modular vaccine design through strategies such as antigen loading, surface engineering, and cytokine-driven modulation. Depending on their cellular source-dendritic cells, macrophages, lymphocytes, or tumor cells-EVs exhibit distinct immunological properties that allow tailored engagement of immune responses. Rather than acting solely as delivery vehicles, they integrate antigen transport, immune activation, and adjuvant effects within a single structure. Recent progress in EV-based cancer vaccine development is reviewed, encompassing vesicle biogenesis, engineering strategies, and delivery optimization, alongside emerging preclinical and clinical evidence supporting their translational potential. Finally, key challenges, including vesicle heterogeneity and manufacturing standardization, are outlined as factors that must be addressed to enable clinical advancement.