A STING-activating nanovaccine for cancer immunotherapy

M Luo, H Wang, Z Wang, H Cai, Z Lu, Y Li, M Du… - Nature …, 2017 - nature.com
M Luo, H Wang, Z Wang, H Cai, Z Lu, Y Li, M Du, G Huang, C Wang, X Chen, MR Porembka
Nature nanotechnology, 2017nature.com
The generation of tumour-specific T cells is critically important for cancer immunotherapy,. A
major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of
antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we
report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a
synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell
response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves …
Abstract
The generation of tumour-specific T cells is critically important for cancer immunotherapy,. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes. This effect is dependent on stimulator of interferon genes (STING), but not the Toll-like receptor or the mitochondrial antiviral-signalling protein (MAVS) pathway. The nanovaccine led to potent tumour growth inhibition in melanoma, colon cancer and human papilloma virus-E6/E7 tumour models. The combination of the PC7A nanovaccine and an anti-PD-1 antibody showed great synergy, with 100% survival over 60 days in a TC-1 tumour model. Rechallenging of these tumour-free animals with TC-1 cells led to complete inhibition of tumour growth, suggesting the generation of long-term antitumour memory. The STING-activating nanovaccine offers a simple, safe and robust strategy in boosting anti-tumour immunity for cancer immunotherapy.
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