STING Nanoagonist Boosts Antitumor Immunity of Therapeutic DNA Vaccines

Abstract

Therapeutic DNA cancer vaccines can stimulate specific immune responses against cancer antigens but often induce suboptimal therapeutic responses. Here, we demonstrate that a manganese-doped silica nanoparticle STING agonist (MSNA) enhances the immune response of plasmid DNA vaccines, promoting the activation and migration of distinct subsets of dendritic cell (DC) and improving antitumor immunity in three animal models. MSNA coadministered with an α-fetoprotein (AFP) encoded plasmid DNA (AFP-DNA) elicited significantly higher AFP-specific CD8 T cell responses than free AFP-DNA. Animals immunized with MSNA-AFP-DNA remained tumor-free in an AFP expressing hepatocellular carcinoma challenge model. MSNA combined with a DNA plasmid encoding the human papillomavirus type 16 oncoproteins E6 and E7 induced potent E7-specific CD8 T cell responses, preventing the growth of E7-expressing solid TC-1 tumors and promoting the shrinkage of E7-expressing skin grafts. These findings together demonstrate that coadministration of MSNA can improve the efficacy of therapeutic DNA vaccines targeting cancer-specific antigens.