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 language | English (US) |
|---|---|
| Pages (from-to) | 648-654 |
| Number of pages | 7 |
| Journal | Nature Nanotechnology |
| Volume | 12 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2017 |
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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 journal › Article
}
TY - JOUR
T1 - A STING-activating nanovaccine for cancer immunotherapy
AU - Luo, Min
AU - Wang, Hua
AU - Wang, Zhaohui
AU - Cai, Haocheng
AU - Lu, Zhigang
AU - Li, Yang
AU - Du, Mingjian
AU - Huang, Gang
AU - Wang, Chensu
AU - Chen, Xiang
AU - Porembka, Matthew R.
AU - Lea, Jayanthi
AU - Frankel, Arthur E.
AU - Fu, Yang Xin
AU - Chen, Zhijian J.
AU - Gao, Jinming
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85018382461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018382461&partnerID=8YFLogxK
U2 - 10.1038/nnano.2017.52
DO - 10.1038/nnano.2017.52
M3 - Article
C2 - 28436963
AN - SCOPUS:85018382461
VL - 12
SP - 648
EP - 654
JO - Nature Nanotechnology
JF - Nature Nanotechnology
SN - 1748-3387
IS - 7
ER -