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A DNA nanodevice-based vaccine for cancer immunotherapy

Nature Materials volume 20, pages 421–430 (2021)Cite this article

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A Publisher Correction to this article was published on 16 September 2020

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Abstract

A major challenge in cancer vaccine therapy is the efficient delivery of antigens and adjuvants to stimulate a controlled yet robust tumour-specific T-cell response. Here, we describe a structurally well defined DNA nanodevice vaccine generated by precisely assembling two types of molecular adjuvants and an antigen peptide within the inner cavity of a tubular DNA nanostructure that can be activated in the subcellular environment to trigger T-cell activation and cancer cytotoxicity. The integration of low pH-responsive DNA ‘locking strands’ outside the nanostructures enables the opening of the vaccine in lysosomes in antigen-presenting cells, exposing adjuvants and antigens to activate a strong immune response. The DNA nanodevice vaccine elicited a potent antigen-specific T-cell response, with subsequent tumour regression in mouse cancer models. Nanodevice vaccination generated long-term T-cell responses that potently protected the mice against tumour rechallenge.

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Fig. 1: Design and characterization of the antigen/adjuvant-functionalized DNA nanodevice vaccine.
Fig. 2: Delivery of nanodevice vaccine to APCs and triggered activation.
Fig. 3: Lymph-node targeting of the nanodevice and the stimulation of CTL response in vivo.
Fig. 4: The nanodevice vaccine inhibits tumour growth and improves survival of tumour-bearing mice.
Fig. 5: DNA Nanodevice-based neoantigen vaccination for cancer immunotherapy.
Fig. 6: The nanodevice vaccine inhibits tumour metastasis and recurrence.

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Data availability

The data that support the findings of this study are available within the paper and its Supplementary Information files. Additional data and files are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the Beijing Municipal Science & Technology Commission (Z191100004819008), the National Basic Research Program of China (2016YFA0201601, 2018YFA0208900), the National Natural Science Foundation of China (21573051, 31700871, 21708004 and 51761145044), the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (21721002), the Key Research Program of Frontier Sciences, CAS, Grant QYZDBSSW-SLH029, the CAS Interdisciplinary Innovation Team and K. C. Wong Education Foundation (GJTD-2018-03) and the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000).

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  1. These authors contributed equally: Shaoli Liu, Qiao Jiang.

Authors and Affiliations

  1. CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China

    Shaoli Liu, Qiao Jiang, Xiao Zhao, Ruifang Zhao, Yuanning Wang, Yiming Wang, Jianbing Liu, Yingxu Shang, Shuai Zhao, Tiantian Wu, Yinlong Zhang, Guangjun Nie & Baoquan Ding

  2. University of Chinese Academy of Sciences, Beijing, China

    Shaoli Liu, Yiming Wang, Yingxu Shang, Shuai Zhao, Tiantian Wu, Guangjun Nie & Baoquan Ding

  3. School of Materials Science and Engineering, Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou, China

    Baoquan Ding

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  1. Shaoli Liu
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Contributions

B.D., Q.J. and S.L. conceived and designed the experiments. S.L., Q.J., Yuanning Wang, S.Z., T.W. and Yiming Wang performed the experiments. S.L., Q.J., J.L., Y.S. and B.D. collected and analysed the data. G.N., X.Z., R.Z. and Y.Z. provided suggestions and technical support on the project. B.D. supervised the project. Q.J., S.L. and B.D. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Baoquan Ding.

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Supplementary Information

Supplementary Figs. 1–37, Tables 1–2 and Note 1.

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Liu, S., Jiang, Q., Zhao, X. et al. A DNA nanodevice-based vaccine for cancer immunotherapy. Nat. Mater. 20, 421–430 (2021). https://doi.org/10.1038/s41563-020-0793-6

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