{"id":"doi:10.1002/advs.202201895","kind":"article","title":"Responsive Multivesicular Polymeric Nanovaccines that Codeliver STING Agonists and Neoantigens for Combination Tumor Immunotherapy","authors":["Su T","Cheng F","Qi J","Zhang Y","Zhou S","Mei L","Fu S","Zhang F","Lin S","Zhu G"],"author_count":10,"year":2022,"published":"2022-06-16","venue":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","cited_by":56,"doi":"10.1002/advs.202201895","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/advs.202201895","archive_url":"https://space-kitty.com/papers/doi:10.1002/advs.202201895","updated":null,"pmid":"35712773","pmcid":"PMC9376841","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC9376841/pdf","abstract":"Immune checkpoint blockade (ICB) has significantly advanced cancer immunotherapy, yet its patient response rates are generally low. Vaccines, including immunostimulant-adjuvanted peptide antigens, can improve ICB. The emerging neoantigens generated by cancer somatic mutations elicit cancer-specific immunity for personalized immunotherapy; the novel cyclic dinucleotide (CDN) adjuvants activate stimulator of interferon genes (STING) for antitumor type I interferon (IFN-I) responses. However, CDN/neoantigen vaccine development has been limited by the poor antigen/adjuvant codelivery. Here, pH-responsive CDN/neoantigen codelivering nanovaccines (NVs) for ICB combination tumor immunotherapy are reported. pH-responsive polymers are synthesized to be self-assembled into multivesicular nanoparticles (NPs) at physiological pH and disassembled at acidic conditions. NPs with high CDN/antigen coloading are selected as NVs for CDN/antigen codelivery to antigen presenting cells (APCs) in immunomodulatory lymph nodes (LNs). In the acidic endosome of APCs, pH-responsive NVs facilitate the vaccine release and escape into cytosol, where CDNs activate STING for IFN-I responses and antigens are presented by major histocompatibility complex (MHC) for T-cell priming. In mice, NVs elicit potent antigen-specific CD8 + T-cell responses with immune memory, and reduce multifaceted tumor immunosuppression. In syngeneic murine tumors, NVs show robust ICB combination therapeutic efficacy. Overall, these CDN/neoantigen-codelivering NVs hold the potential for ICB combination tumor immunotherapy.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Responsive Multivesicular Polymeric Nanovaccines that Codeliver STING Agonists and Neoantigens for Combination Tumor Immunotherapy\" by Su T, Cheng F, Qi J et al., https://doi.org/10.1002/advs.202201895, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}