A STING-activating nanovaccine for cancer immunotherapy

Nat Nanotechnol. 2017 Jul;12(7):648-654. doi: 10.1038/nnano.2017.52. Epub 2017 Apr 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cancer Vaccines* / chemistry
  • Cancer Vaccines* / immunology
  • Cancer Vaccines* / pharmacology
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunotherapy
  • Membrane Proteins* / chemistry
  • Membrane Proteins* / immunology
  • Membrane Proteins* / pharmacology
  • Mice
  • Mice, Knockout
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Neoplasm Proteins / immunology
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*
  • THP-1 Cells


  • Adaptor Proteins, Signal Transducing
  • Cancer Vaccines
  • IPS-1 protein, mouse
  • Membrane Proteins
  • Neoplasm Proteins
  • STING1 protein, human