Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Acta Biomater. 2023 Mar 1;158:535-546. doi: 10.1016/j.actbio.2022.12.070. Epub 2023 Jan 9.
Vaccination shows great promise in cancer immunotherapy. However, the induction of robust and broad therapeutic CD8 T cell immunity against tumors is challenging due to the essential heterogenicity of tumor antigen expression. Recently, bioinspired materials have reshaped the field of cancer nanomedicine. Herein, a bioinspired nanofibrous trivalent peptide hydrogel vaccine was constructed using the spontaneous supramolecular co-assembly of three antigenic epitope-conjugated peptides, which could mimic the fibrillar structure and biological function of the extracellular matrix and naturally occurring protein assembly. The hydrogel vaccine could be accurately and flexibly adjusted to load each antigenic peptide at a defined ratio, which facilitated the antigen presentation of dendritic cells and significantly improved the initiation of CD8 T cell response and the secretion of interferon-γ (IFN-γ). C57BL/6 mice were immunized with the trivalent peptide hydrogel vaccine, where it elicited a high broad-spectrum antitumor CD8 T cell response that significantly inhibited the growth of B16 tumors in the absence of additional immunoadjuvants or delivery systems. In summary, the supramolecular assembly of triple antigenic epitope-conjugated peptides offers a simple, customizable, and versatile approach for the development of cancer vaccines with remarkable therapeutic efficacy, thereby providing a highly versatile platform for the application of personalized multivalent tumor vaccines. STATEMENT OF SIGNIFICANCE: (1) We report a feasible, versatile and bioinspired approach to manufacture a multivalent peptide-based hydrogel cancer vaccine in the absence of additional adjuvants, which closely mimics immune niches, co-delivers antigen epitopes, greatly promotes antigen presentation to DCs and their subsequent homing to dLNs and elicits a broad-spectrum antitumor CD8 T cell response, resulting in significant inhibition of B16 tumor growth. (2) This feasible and efficient co-assembly strategy provides an attractive platform for engineering a range of multivalent vaccines at defined ratios to further enhance antigen-specific T cell responses. This approach may also be used for personalized immunotherapy with neo-epitopes.
疫苗接种在癌症免疫疗法中显示出巨大的前景。然而，由于肿瘤抗原表达的固有异质性，诱导针对肿瘤的强大和广泛的治疗性 CD8 T 细胞免疫具有挑战性。最近，仿生材料重塑了癌症纳米医学领域。在此，使用三种抗原表位偶联肽的自发超分子共组装构建了仿生纳米纤维三价肽水凝胶疫苗，该水凝胶可以模拟细胞外基质和天然蛋白质组装的纤维状结构和生物学功能。水凝胶疫苗可以精确且灵活地调节以按定义的比例装载每种抗原肽，这有利于树突状细胞的抗原呈递，并显著提高 CD8 T 细胞反应的启动和干扰素-γ（IFN-γ）的分泌。C57BL/6 小鼠用三价肽水凝胶疫苗免疫，该疫苗引发了广谱抗肿瘤 CD8 T 细胞反应，在没有额外免疫佐剂或递送系统的情况下，显著抑制了 B16 肿瘤的生长。总之，三价抗原表位偶联肽的超分子组装为开发具有显著治疗功效的癌症疫苗提供了一种简单、可定制和多功能的方法，从而为个性化多价肿瘤疫苗的应用提供了一个高度通用的平台。意义声明：（1）我们报告了一种可行的、多功能的仿生方法来制造一种无额外佐剂的多价肽基水凝胶癌症疫苗，该疫苗紧密模拟免疫生态位，共同递呈抗原表位，极大地促进了抗原向 DC 的呈递及其随后向 dLNs 的归巢，并引发广谱抗肿瘤 CD8 T 细胞反应，导致 B16 肿瘤生长受到显著抑制。（2）这种可行且高效的共组装策略为在定义的比例下工程多种多价疫苗提供了一个有吸引力的平台，以进一步增强抗原特异性 T 细胞反应。这种方法也可用于具有新表位的个性化免疫疗法。
