Engineering Polymeric Prodrug Nanoplatform for Vaccination Immunotherapy of Cancer
- 27 May 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Nano Letters
- Vol. 20 (6), 4393-4402
- https://doi.org/10.1021/acs.nanolett.0c01140
Abstract
Neoantigen-based cancer vaccines are promising for boosting cytotoxic T lymphocytes (CTLs) 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 STING agonist and neoantigen into one single nanoplatform. The nanovaccines efficiently accumulated at the lymph nodes for promoting DCs uptake and facilitating cytosol release of the neoantigens. Meanwhile, the STING agonist activated the STING pathway in the DCs to elicit interferon β 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 4T1 breast tumor model.Keywords
Funding Information
- National Natural Science Foundation of China (31671024, 51873228, 81521005)
- Natural Science Foundation of Shandong Province (ZR2019LZL020)
- State Key Laboratory of Drug Research (SIMM2004KF-04)
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