Cancer vaccines have been developed as a promising way to boost cancer immunity. However, their clinical potency is often limited due to the imprecise delivery of tumor antigens. To overcome this problem, we conjugated an endogenous Toll-like receptor (TLR)2/6 ligand, UNE-C1, to human papilloma virus type 16 (HPV-16)-derived peptide antigen, E7, and found that the UNE-C1-conjugated cancer vaccine (UCV) showed significantly enhanced antitumor activity compared with the noncovalent combination of UNE-C1 and E7. The combination of UCV with PD-1 blockades further augmented its therapeutic efficacy. Specifically, the conjugation of UNE-C1 to E7 enhanced its retention in inguinal draining lymph nodes, the specific delivery to dendritic cells and E7 antigen-specific T cell responses, and antitumor efficacy compared with the noncovalent combination of the two peptides. These findings suggest the potential of UNE-C1 derived from human cysteinyl-tRNA synthetase 1 as a unique vehicle for the specific delivery of cancer antigens to antigen-presenting cells via TLR2/6 for the improvement of cancer vaccines.

中文翻译：

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通过半胱氨酰-tRNA 合成酶 1 衍生的内源性 TLR2/6 配体将癌症疫苗特异性靶向抗原呈递细胞


癌症疫苗已被开发为增强癌症免疫力的一种有前景的方法。然而，由于肿瘤抗原的不精确传递，它们的临床效力往往受到限制。为了克服这个问题，我们将内源性 Toll 样受体 (TLR)2/6 配体 UNE-C1 与人乳头瘤病毒 16 型 (HPV-16) 衍生肽抗原 E7 缀合，并发现 UNE-C1与 UNE-C1 和 E7 的非共价组合相比，结合癌症疫苗 (UCV) 显示出显着增强的抗肿瘤活性。 UCV 与 PD-1 阻断剂的组合进一步增强了其治疗效果。具体而言，与两种肽的非共价组合相比，UNE-C1 与 E7 的缀合增强了其在腹股沟引流淋巴结中的保留、对树突细胞的特异性递送和 E7 抗原特异性 T 细胞反应以及抗肿瘤功效。这些发现表明，源自人半胱氨酰-tRNA合成酶1的UNE-C1有潜力作为一种独特的载体，通过TLR2/6将癌症抗原特异性递送至抗原呈递细胞，从而改进癌症疫苗。