A STING-Activating Nanovaccine for Cancer Immunotherapy

By Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen and 6 more. Nature Nanotechnology, 2017

765 citations recorded by the source corpus.

Generation of tumor-specific T cells is critically important for cancer immunotherapy1,2. A major challenge in achieving a robust T cell response is the spatio-temporal orchestration of antigen cross-presentation in antigen presenting cells (APCs) with innate stimulation. Here we report a minimalist nanovaccine by a simple physical mixture of an antigen with a synthetic polymeric nanoparticle, PC7A NP, which generated a strong cytotoxic T cell response with low systemic cytokine expression. Mechanistically, PC7A NP achieved efficient cytosolic delivery of tumor antigens to APCs in draining lymph nodes leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes. This effect was dependent on STING but not Toll-like receptor or MAVS pathway. Nanovaccine produced potent tumor growth inhibition in melanoma, colon cancer, and human papilloma virus-E6/E7 tumor models. Combination of PC7A nanovaccine with an anti-PD-1 antibody showed great synergy with 100% survival over 60 days in a TC-1 tumor model. Rechallenging of these tumor-free animals with TC-1 cells led to complete inhibition of tumor growth, suggesting generation of long-term antitumor memory. The STING-activating nanovaccine offers a simple, safe and robust strategy in boosting anti-tumor immunity for cancer immunotherapy.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/7b5c455ffe55e7e10e425b8e0cd9296685a28e66

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Citations in the corpus

Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery. (2019, neutral): “Recent work suggests that lipid or polymeric carriers could activate type I IFN while chemically modified mRNA does not induce type I IFN activation.(190) Rapid release of mRNA into the cytoplasm together with activation of a type I IFN using delivery materials may result in a kinetic that improves ”
Tumor Targeting via EPR: Strategies to Enhance Patient Responses (2018, background): “Combination with an immune checkpoint inhibitor for programmed cell death (PD-1) resulted in synergistically improved anti-tumor response and survival rate in tumor bearing mice [181].”