A STING-activating nanovaccine for cancer immunotherapy

Nature Nanotechnology 12, 648 (2017). doi:10.1038/nnano.2017.52 Authors: Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R. Porembka, Jayanthi Lea, Arthur E. Frankel, Yang-Xin Fu, Zhijian J. Chen & Jinming Gao 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 o...
Source: Nature Nanotechnology - Category: Nanotechnology Authors: Tags: Letter Source Type: research