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.

癌症疫苗治疗的一个主要挑战是有效递送抗原和佐剂以刺激受控但强大的肿瘤特异性 T 细胞反应。在这里，我们描述了一种结构明确的 DNA 纳米装置疫苗，它是通过在管状 DNA 纳米结构的内腔中精确组装两种类型的分子佐剂和抗原肽而产生的，这种疫苗可以在亚细胞环境中被激活以触发 T 细胞激活和癌症细胞毒性. 纳米结构外的低 pH 响应 DNA“锁定链”的整合使得疫苗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。DNA 纳米装置疫苗引发了有效的抗原特异性 T 细胞反应，随后在小鼠癌症模型中出现肿瘤消退。