A DNA nanodevice-based vaccine for cancer immunotherapy

• Published in: Nature materials 2021-03, Vol.20 (3), p.421-430
• Main Authors: Liu, Shaoli, Jiang, Qiao, Zhao, Xiao, Zhao, Ruifang, Wang, Yuanning, Wang, Yiming, Liu, Jianbing, Shang, Yingxu, Zhao, Shuai, Wu, Tiantian, Zhang, Yinlong, Nie, Guangjun, Ding, Baoquan
• Format: Article
• Language: English
• Subjects: 631/67/1059/2325; 639/301/357/341; 639/925/926/1048; Adjuvants; Adjuvants, Immunologic - administration & dosage; Animals; Antigen Presentation; Antigens; Bacteriophage M13 - genetics; Biocompatibility; Biomaterials; Cancer; Cancer Vaccines - administration & dosage; Cancer Vaccines - genetics; Cancer Vaccines - immunology; Chemistry and Materials Science; Condensed Matter Physics; Cytotoxicity; Cytotoxicity Tests, Immunologic; Dendritic Cells - drug effects; Dendritic Cells - immunology; Deoxyribonucleic acid; DNA; Hydrogen-Ion Concentration; Immune response; Immune system; Immunotherapy; Immunotherapy - methods; Locking; Lymphatic Metastasis - prevention & control; Lymphocytes; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Lysosomes; Materials Science; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; Mice; Mice, Inbred C57BL; Nanostructure; Nanotechnology; Nanotechnology devices; Optical and Electronic Materials; Robust control; Toxicity; Tumors; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology
• ISSN: 1476-1122; 1476-4660
• DOI: 10.1038/s41563-020-0793-6

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. 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.