Dendritic-cell-derived exosomes (DEX) secreted after dendritic cell loading with tumor peptides were found to mediate tumor rejection in mice. This observation prompted us to demonstrate that MHC class I/peptide complexes harbored onto exosomal membranes were capable of priming cytotoxic T cells and to mediate rejection of tumors expressing the relevant antigens. Moreover, DEX also promote NK cell activation in immunocompetent mice and NK cell-dependent antitumor effects. The first Phase I trial using DEX to immunize melanoma patients revealed the feasibility of DEX production in stage IV melanoma, their safety in long-term follow up and their bioactivity in vivo.