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.

Original languageEnglish (US)
Pages (from-to)648-654
Number of pages7
JournalNature Nanotechnology
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2017

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interferon
Interferons
genes
Tumors
tumors
Genes
cancer
antigens
T-cells
Antigens
cells
Interferon Type I
Toll-Like Receptors
Neoplasm Antigens
lymphatic system
Viruses
immunity
viruses
Antiviral Agents
drainage

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

Cite this

A STING-activating nanovaccine for cancer immunotherapy. / Luo, Min; Wang, Hua; Wang, Zhaohui; Cai, Haocheng; Lu, Zhigang; Li, Yang; Du, Mingjian; Huang, Gang; Wang, Chensu; Chen, Xiang; Porembka, Matthew R.; Lea, Jayanthi; Frankel, Arthur E.; Fu, Yang Xin; Chen, Zhijian J.; Gao, Jinming.

In: Nature Nanotechnology, Vol. 12, No. 7, 01.07.2017, p. 648-654.

Research output: Contribution to journalArticle

Luo M, Wang H, Wang Z, Cai H, Lu Z, Li Y et al. A STING-activating nanovaccine for cancer immunotherapy. Nature Nanotechnology. 2017 Jul 1;12(7):648-654. https://doi.org/10.1038/nnano.2017.52
Luo, Min ; Wang, Hua ; Wang, Zhaohui ; Cai, Haocheng ; Lu, Zhigang ; Li, Yang ; Du, Mingjian ; Huang, Gang ; Wang, Chensu ; Chen, Xiang ; Porembka, Matthew R. ; Lea, Jayanthi ; Frankel, Arthur E. ; Fu, Yang Xin ; Chen, Zhijian J. ; Gao, Jinming. / A STING-activating nanovaccine for cancer immunotherapy. In: Nature Nanotechnology. 2017 ; Vol. 12, No. 7. pp. 648-654.
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