Engineered dendritic cells-derived extracellular vesicles for cancer immunotherapy

Extracellular vesicles (EVs) have emerged as a cell-free therapeutic approach, garnering increasing attention for their potential to enhance the safety and efficacy of immunotherapy. This interest is primarily driven by the biocompatibility and cell/tissue tropism inherent to EVs, but also due to their reconfigurable content. This, termed as cargo, may comprise bioactive molecules as proteins, lipids, and nucleic acids that play a pivotal role in mediating intercellular communication. In particular, dendritic cells-derived extracellular vesicles (DC-EVs) facilitate the transfer of critical components, like antigens and immune-regulatory factors, and due to the expression of major histocompatibility complexes and co-stimulatory molecules on their surface can activate T cells, thereby modulating the immune response. Additionally, DC-EVs can be engineered to transport tumorspecific antigens, cytokines, or other agents in order to strength their immunotherapeutic potential, and even be used in vaccines formulation. In this review, the latest advancements in engineering DC-EVs to improve their immunotherapeutic potential is discussed in detail, while also addressing current challenges associated with DCEVs therapies.