Abstract：
Therapeutic cancer vaccines are among the first FDA-approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph-node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated-DCs homing from the periphery to the LNs, an injectable hydrogel-based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine \"hitchhiking\" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve \"antigen anchoring\" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and \"hitchhiking\" subcutaneous Migrated-DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six-fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN-resident APCs via the \"One-to-Many\" strategy (One Migrated-DC corresponding to Many LN-resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation.
摘要：
治疗性癌症疫苗是FDA批准的首批癌症免疫疗法之一。其中,它仍然是一个主要的挑战，以实现强大的淋巴结（LN）积累。然而,由于淋巴管的独特结构，将货物运送到LN是困难的，和临床反应在很大程度上令人失望。在这里，受从外围到LN的迁移DC归巢的启发，描述了一种可注射的基于水凝胶的多肽疫苗系统，用于增强免疫刺激功效，这可能会在DC上形成疫苗的局部利基“搭便车”。由水凝胶中的亲脂性DSPE结构域修饰的OVA肽自发地插入细胞膜中以在体内实现DC上的“抗原锚定”。总的来说,OVA肽通过招募和“搭便车”皮下迁移DC来实现主动访问LN。值得注意的是,已证明,与游离OVA肽相比,复合水凝胶将LN靶向功效增强约6倍。然后，OVA肽可以在LN内典型的酸性微环境下从细胞表面去除，通过“一对多”策略(一个迁移DC对应于许多LN驻留APC)进一步与LN驻留APC共享它们，从而激活强大的免疫刺激。此外，所述水凝胶疫苗在黑素瘤中表现出显著的肿瘤生长抑制并抑制肺转移性结节形成。
