Improved antigen cross-presentation by polyethyleneimine-based nanoparticles

Purpose: In the development of therapeutic vaccines against cancer, it is important to design strategies for antigen cross-presentation to stimulate cell-mediated immune responses against tumor antigens. Methods: We developed a polyethyleneimine (PEI)-based protein antigen delivery system to promote cross-presentation through the major histocompatibility complex (MHC) I pathway using ovalbumin (OVA) as a model antigen. PEIs formed nanoparticles with OVA by electrostatic interactions, as demonstrated by electrophoresis analysis, scanning electron microscopy, and photon correlation spectroscopy analysis. Results: The nanoparticles were used to stimulate mouse bone marrow-derived dendritic cells in vitro and resulted in significantly more OVA_257-264/MHC I complex presentation on dendritic cell surfaces. The activated dendritic cells interacted specifically with RF33.70 to stimulate interleukin-2 secretion. The cross-presentation promoting effect was more prominent in dendritic cells that had been cultured for longer periods of time (13 days). Further studies comparing the antigen presentation efficacies by other polyanionic agents, such as PLL or lysosomotropic agents, suggested that the unique "proton sponge effect" of PEI facilitated antigen escape from the endosome toward the MHC I pathway. Conclusion: Such a PEI-based nanoparticle system may have the potential to be developed into an effective therapeutic vaccine delivery system.