Exosomes as novel therapeutic nanodevices

Exosomes are small vesicles (60 to 100 nm) that are released by many cell types. Their heterogeneous protein and lipid compositions, in addition to their enduring physicochemical features have led to the idea of using these natural vesicles as nanodevices for the development of new therapeutic applications. The first exosome-based nanodevices evaluated in the clinic consisted of autologous dexosomes (patient-specific exosomes released by dendritic cells and loaded with tumor antigen-derived peptides). They were tested in two phase I trials as immunotherapeutic regimens for melanoma and nonsmall-cell lung cancer. These studies revealed that dexosome immunotherapy was feasible, safe and led to the induction of both innate and adaptive immune responses, disease stabilization and long-term survival for several patients. The recent steps made towards transforming exosomes into product candidates for immunotherapy are summarized. In addition, recent developments in the field of exosome research that we believe will lead to improved and/or new therapeutic applications are highlighted. For example, a technology known as exosome display can be utilized to develop genetic vaccines that could induce exosome-mediated immunity without requiring the preparation of patient-derived exosomes.