期刊
NANO LETTERS
卷 20, 期 6, 页码 4393-4402出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c01140
关键词
Polymeric prodrug; Neoantigen; Adaptive immune response; Personalized immunotherapy; Nanoparticles
类别
资金
- National Natural Science Foundation of China [51873228, 31671024, 81521005]
- Natural Science Foundation of Shandong Province [ZR2019LZL020]
- State Key Laboratory of Drug Research [SIMM2004KF-04]
Neoantigen-based cancer vaccines are promising for boosting cytotoxic T lymphocyte (CTL) responses. However, the therapeutic effect of cancer vaccines is severely blunted by functional suppression of the dendritic cells (DCs). Herein, we demonstrated an acid-responsive polymeric nanovaccine for activating the stimulator of interferon genes (STING) pathway and improving cancer immunotherapy. The nanovaccines were fabricated by integrating an acid-activatable polymeric conjugate of the STING agonist and neoantigen into one single nanoplatform. The nanovaccines efficiently accumulated at the lymph nodes for promoting DC uptake and facilitating cytosol release of the neoantigens. Meanwhile, the STING agonist activated the STING pathway in the DCs to elicit interferon-beta secretion and to boost T-cell priming with the neoantigen. The nanovaccine dramatically inhibited tumor growth and occurrence of B16-OVA melanoma and 4T1 breast tumors in immunocompetent mouse models. Combination immunotherapy with the nanovaccines and anti-PD-L1 antibody demonstrated further improved antitumor efficacy in a 4T1 breast tumor model.
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