# Responsive Multivesicular Polymeric Nanovaccines that Codeliver STING Agonists and Neoantigens for Combination Tumor Immunotherapy

Article · Su T, Cheng F, Qi J, Zhang Y, Zhou S, Mei L, Fu S, Zhang F, Lin S, Zhu G

- Archive id: doi:10.1002/advs.202201895
- Published: 2022-06-16
- Venue: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
- DOI: https://doi.org/10.1002/advs.202201895
- PMID: 35712773
- PMCID: PMC9376841
- Citations: 56
- Source URL: https://doi.org/10.1002/advs.202201895
- PDF: https://europepmc.org/articles/PMC9376841/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines)

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