Exosomes are secreted membrane nanovesicles of endosomal origin and are considered as potential cancer vaccine vectors. Phase I clinical trials have been successfully conducted with tumor peptide-loaded exosomes derived from dendritic cells (dexosomes) and a phase II clinical trial is currently ongoing. However, much is still unknown regarding the in vivo role of dexosomes and if the immunogenicity of dexosomes can be enhanced. We have previously reported that dexosomes induce CD4+ T cell responses in a B cell dependent manner, suggesting that immunizing with dexosomes only carrying T cell peptides induce suboptimal immune responses. Here we show that CD8+ T cell responses were induced in vivo when mice were immunized with protein, but not peptide, loaded dexosomes. We could also show that the cytotoxic T cell response was totally dependent on CD4+ T cells and, interestingly, also on B cells. Mice deficient in complement activation and antigen shuttling by B cells have lower responses to protein-loaded dexosomes showing involvement of these B cell mediated mechanisms. Finally, protein-loaded dexosomes were superior in protecting against tumor growth. In conclusion, proper activation of CD4+ T and B cells need to be considered when designing cancer vaccines to ensure full potential of the treatment.
- Copyright © 2013 by The American Association of Immunologists, Inc.