STING Nanoagonist\nBoosts Antitumor Immunity of Therapeutic\nDNA Vaccines

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