A DNA nanodevice-based vaccine for cancer immunotherapy


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.

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.

Change history

  • 16 September 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.


  1. 1.

    Mellman, I., Coukos, G. & Dranoff, G. Cancer immunotherapy comes of age. Nature 480, 480–489 (2011).

    CAS  Article  Google Scholar 

  2. 2.

    Kreiter, S. et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520, 692–696 (2015).

    CAS  Article  Google Scholar 

  3. 3.

    Liu, H. et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507, 519–522 (2014).

    CAS  Article  Google Scholar 

  4. 4.

    Ott, P. A. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547, 217–221 (2017).

    CAS  Article  Google Scholar 

  5. 5.

    Sahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222–226 (2017).

    CAS  Article  Google Scholar 

  6. 6.

    Banchereau, J. & Palucka, A. K. Dendritic cells as therapeutic vaccines against cancer. Nat. Rev. Immunol. 5, 296–306 (2005).

    CAS  Article  Google Scholar 

  7. 7.

    Zhu, G., Zhang, F., Ni, Q., Niu, G. & Chen, X. Efficient nanovaccine delivery in cancer immunotherapy. ACS Nano 11, 2387–2392 (2017).

    CAS  Article  Google Scholar 

  8. 8.

    Hamanishi, J. et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl Acad. Sci. USA 104, 3360–3365 (2007).

    CAS  Article  Google Scholar 

  9. 9.

    Kuai, R., Ochyl, L. J., Bahjat, K. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat. Mater. 16, 489–496 (2017).

    CAS  Article  Google Scholar 

  10. 10.

    Luo, M. et al. A STING-activating nanovaccine for cancer immunotherapy. Nat. Nanotechnol. 12, 648–654 (2017).

    CAS  Article  Google Scholar 

  11. 11.

    Li, A. W. et al. A facile approach to enhance antigen response for personalized cancer vaccination. Nat. Mater. 17, 528–534 (2018).

    CAS  Article  Google Scholar 

  12. 12.

    Zhu, G. et al. Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy. Nat. Commun. 8, 1482 (2017).

    Article  Google Scholar 

  13. 13.

    Min, Y. et al. Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy. Nat. Nanotechnol. 12, 877–882 (2017).

    CAS  Article  Google Scholar 

  14. 14.

    Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831–834 (2012).

    CAS  Article  Google Scholar 

  15. 15.

    Li, S. et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat. Biotechnol. 36, 258–264 (2018).

    CAS  Article  Google Scholar 

  16. 16.

    Jiang, Q., Liu, S., Liu, J., Wang, Z.-G. & Ding, B. Rationally designed DNA-origami nanomaterials for drug delivery in vivo. Adv. Mater. 31, 1804785 (2019).

    CAS  Article  Google Scholar 

  17. 17.

    Liu, L. et al. Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320, 379–381 (2008).

    CAS  Article  Google Scholar 

  18. 18.

    Latz, E. et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat. Immunol. 5, 190–198 (2004).

    CAS  Article  Google Scholar 

  19. 19.

    Reed, S. G., Bertholet, S., Coler, R. N. & Friede, M. New horizons in adjuvants for vaccine development. Trends Immunol. 30, 23–32 (2009).

    CAS  Article  Google Scholar 

  20. 20.

    Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).

    CAS  Article  Google Scholar 

  21. 21.

    Green, L. N., Amodio, A., Subramanian, H. K. K., Ricci, F. & Franco, E. pH-driven reversible self-assembly of micron-scale DNA scaffolds. Nano Lett. 17, 7283–7288 (2017).

    CAS  Article  Google Scholar 

  22. 22.

    Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534, 396–401 (2016).

    Article  Google Scholar 

  23. 23.

    Barber, D. L., Wherry, E. J. & Ahmed, R. Cutting edge: rapid in vivo killing by memory CD8 T cells. J. Immunol. 171, 27–31 (2003).

    CAS  Article  Google Scholar 

  24. 24.

    Hailemichael, Y. et al. Persistent antigen at vaccination sites induces tumor-specific CD8+ T cell sequestration, dysfunction and deletion. Nat. Med. 19, 465–472 (2013).

    CAS  Article  Google Scholar 

  25. 25.

    Verdegaal, E. M. E. et al. Neoantigen landscape dynamics during human melanoma–T cell interactions. Nature 536, 91–95 (2016).

    CAS  Article  Google Scholar 

  26. 26.

    Conniot, J. et al. Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators. Nat. Nanotechnol 14, 891–901 (2019).

    CAS  Article  Google Scholar 

  27. 27.

    Kaczanowska, S., Joseph, A. M. & Davila, E. TLR agonists: our best frenemy in cancer immunotherapy. J. Leukoc. Biol. 93, 847–863 (2013).

    CAS  Article  Google Scholar 

  28. 28.

    Liu, Y. et al. Tumor exosomal RNAs promote lung pre-metastatic niche formation by activating alveolar epithelial TLR3 to recruit neutrophils. Cancer Cell 30, 243–256 (2016).

    Article  Google Scholar 

  29. 29.

    Praetorius, F. et al. Biotechnological mass production of DNA origami. Nature 552, 84–87 (2017).

    CAS  Article  Google Scholar 

  30. 30.

    Douglas, S. M., Chou, J. J. & Shih, W. M. DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc. Natl Acad. Sci. USA 104, 6644–6648 (2007).

    CAS  Article  Google Scholar 

Download references


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).

Author information




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.

Corresponding author

Correspondence to Baoquan Ding.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

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

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, S., Jiang, Q., Zhao, X. et al. A DNA nanodevice-based vaccine for cancer immunotherapy. Nat. Mater. (2020). https://doi.org/10.1038/s41563-020-0793-6

Download citation


Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing