Cationic synthetic long peptides-loaded nanogels: An efficient therapeutic vaccine formulation for induction of T-cell responses

Abstract

Recent studies have shown a high potency of protein-based vaccines for cell-mediated cancer immunotherapy. However, due to their poor cellular uptake, efficient immune responses with soluble protein antigens are often not observed. As a result of superior cellular uptake, nanogels loaded with antigenic peptides were investigated in this study as carrier systems for cancer immunotherapy. Different synthetic long peptides (SLPs) containing the CTL and CD4+ T-helper (Help) epitopes were synthesized and covalently conjugated via disulfide bonds to the polymeric network of cationic dextran nanogels. Cationic nanogels with a size of 210 nm, positive zeta potential (+24 mV) and high peptide loading content (15%) showed triggered release of the loaded peptides under reducing conditions. An in vitro study demonstrated the capability of cationic nanogels to maturate dendritic cells (DCs). Importantly, covalently SLP-loaded nanogels adjuvanted with poly(I:C) showed superior CD8+ T cell responses compared to soluble peptides and nanogel formulations with physically loaded peptides both in vitro and in vivo. In conclusion, covalently SLPs-loaded cationic nanogels are a promising system to provoke immune responses for therapeutic cancer vaccination.