STING Nanoagonist Boosts Antitumor Immunity of Therapeutic DNA Vaccines

Authors:
Publisher website
Google Scholar
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 alpha-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.
Funding Information
  • National Health and Medical Research Council (APP1107356, APP1124265, APP1125794, APP1173927)
  • Australian Research Council (LE150100067)
  • Science and Technology Commission of Shanghai Municipality (21PJ1404500)
  • National Natural Science Foundation of China (32101146)
  • Garnett Passe and Rodney Williams Memorial Foundation
  • University of Queensland (UQECR2058369)
  • Chinese Academy of Sciences (GJHZ2072)
  • Shanghai Shuguang Program (21SG39)
  • School of Medicine, Shanghai University (22820574)
  • Shanghai Excellent Overseas Young Scientists
  • Queensland Biomedical Assistance Fund (2017003021)
  • Merchant Foundation and the Metal Manufacturing Pty Ltd
  • Gallipoli Medical Research
  • Zelman Cowan Academic Initiative

This publication has 34 references indexed in Scilit: