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

Year: 2022

Type: article

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.

Source: Advanced Science

DOI: 10.1002/advs.202201895

Authors: Ting Su, Furong Cheng, Jialong Qi, Yu Zhang, Shurong Zhou, Lei Mei, Shiwei Fu, Fuwu Zhang, Shuibin Lin, Guizhi Zhu

Institutions: Sun Yat-sen University, Virginia Commonwealth University, The First Affiliated Hospital, Sun Yat-sen University, VCU Massey Comprehensive Cancer Center, University of Miami, Dr. John T. Macdonald Foundation

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,200

Funders: Virginia Commonwealth University, METAvivor, National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Norges Idrettshøgskole, National Institutes of Health, Center for Clinical and Translational Research, Basic and Applied Basic Research Foundation of Guangdong Province, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, Congressionally Directed Medical Research Programs

OpenAlex ID: W4283030510