Journal
NATURE MATERIALS
Volume 20, Issue 3, Pages 421-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41563-020-0793-6
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Funding
- Beijing Municipal Science & Technology Commission [Z191100004819008]
- National Basic Research Program of China [2016YFA0201601, 2018YFA0208900]
- National Natural Science Foundation of China [21573051, 31700871, 21708004, 51761145044]
- Science Fund for Creative Research Groups of the National Natural Science Foundation of China [21721002]
- Key Research Program of Frontier Sciences, CAS [QYZDBSSW-SLH029]
- CAS Interdisciplinary Innovation Team
- K. C. Wong Education Foundation [GJTD-2018-03]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB36000000]
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A DNA nanodevice vaccine has been developed to stimulate a tumor-specific cytotoxic T lymphocyte response, leading to inhibition of tumor growth and prevention of metastasis. The vaccine utilizes molecular adjuvants and antigen peptides within a tubular DNA nanostructure to trigger T-cell activation and cancer cytotoxicity, showing promising results in mouse cancer models. The vaccination generates long-term T-cell responses which effectively protect against tumor rechallenge.
A DNA nanodevice vaccine has been developed and utilized to stimulate a tumour-specific cytotoxic T lymphocyte response in vivo, leading to the inhibition of tumour growth as well as prevention of metastasis. 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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