CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Mater. 2021 Mar;20(3):421-430. doi: 10.1038/s41563-020-0793-6. Epub 2020 Sep 7.
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.
在癌症疫苗治疗中，一个主要的挑战是如何有效地将抗原和佐剂递送到体内，以刺激可控但强烈的肿瘤特异性 T 细胞反应。在这里，我们描述了一种结构明确的 DNA 纳米器件疫苗，它通过精确组装两种类型的分子佐剂和抗原肽在管状 DNA 纳米结构的内腔中，在亚细胞环境中被激活后可以触发 T 细胞的激活和肿瘤细胞毒性。在纳米结构外整合低 pH 响应性 DNA“锁定链”，使得疫苗可以在抗原呈递细胞的溶酶体中打开，暴露佐剂和抗原以激活强烈的免疫反应。该 DNA 纳米器件疫苗引发了强烈的抗原特异性 T 细胞反应，随后在小鼠癌症模型中观察到肿瘤消退。纳米器件疫苗接种产生了长期的 T 细胞反应，有效地保护了小鼠免受肿瘤再挑战。
