Reduction-Sensitive Protein Nanogels Enhance Uptake of Model and Tumor Lysate Antigens In Vitro by Mouse- and Human-Derived Dendritic Cells.

Peptides and proteins represent an emerging class of powerful therapeutics. Peptide and protein nanogels are attractive carriers for the transport and delivery of biologically active peptides and proteins because they allow essentially quantitative encapsulation of these biologics. One interesting field of use of peptide and protein nanogels is the transport of antigens and adjuvants in cancer immunotherapy. This study demonstrates the use of reduction-sensitive protein nanogels for the delivery of ovalbumin and oxidized tumor lysate-based antigens to mouse and human-donor-derived dendritic cells. Challenging mouse-derived and human dendritic cells with reduction-sensitive ovalbumin nanogels was found to significantly enhance antigen uptake as compared to the use of the corresponding free protein antigen. The experiments with mouse-derived dendritic cells further showed that the administration of ovalbumin in the form of reduction-sensitive nanogels enhanced dendritic cell maturation as well as the presentation of the SIINFEKL epitope as compared to experiments that use free ovalbumin. In addition to ovalbumin as a model antigen, the feasibility of reduction-sensitive nanogels was also demonstrated for the delivery of oxidized, whole tumor lysate-based cancer antigens. In experiments with dendritic cells harvested from human donors, dendritic cell uptake of the oxidized tumor lysate antigen was significantly enhanced in experiments that used oxidized tumor lysate nanogels as compared to the free antigen.