Transplantation of immune cells manipulated in vitro to dictate immune responses in the body is promising in cancer immunotherapy. However, this approach suffers from low cell survival after administration, insufficient cell homing to lymph nodes, and off-target. Here we demonstrate an injectable and self-assembled poly(l-valine) hydrogel as the delivery carrier of cargoes including antigen and immunopotentiator for DCs modulation. Our results indicate the vaccine formulation composed of tumor cell lysates (TCL), TLR3 agonist, poly(I:C) and polypeptide hydrogel can robustly recruit, activate and mature DCs in vitro and in vivo by sustained release of TCL and poly(I:C). Hydrogel as the delivery system significantly improves antigen persistence at the injection site and antigen drainage to lymph nodes. Strikingly, subcutaneous injection of hydrogel-based vaccine formulations in melanoma-bearing mice elicits good antitumor efficiency by evoking strong cytotoxic T-lymphocyte immune response. Hydrogel vaccine significantly promotes the production of CD8⁺ T cells in draining lymph nodes and tumor infiltrating T-lymphocytes. These findings suggest that in vivo program of DCs by injectable polypeptide hydrogel encapsulated with antigen and immunopentiator is able to direct immune responses against cancer. Our study also implies that such a hydrogel may serve as a multifunctional delivery platform of vaccines.

在癌症免疫疗法中，体外操纵以指导体内免疫反应的免疫细胞的移植是有希望的。但是，这种方法的缺点是给药后细胞存活率低，细胞归巢至淋巴结不足以及脱靶。在这里，我们证明了可注射和自组装的聚（1-缬氨酸）水凝胶作为货物的递送载体，包括用于DC调节的抗原和免疫增强剂。我们的结果表明肿瘤细胞裂解物（TCL），TLR3激动剂组成的疫苗制剂，聚（I：C）和多肽水凝胶可以鲁棒地招募，激活和成熟的DCs在体外和体内通过持续释放TCL和poly（I：C）。水凝胶作为输送系统可显着改善注射部位的抗原持久性和抗原向淋巴结的排泄。引人注目的是，在带有黑色素瘤的小鼠中皮下注射基于水凝胶的疫苗制剂会引起强烈的细胞毒性T淋巴细胞免疫反应，从而产生良好的抗肿瘤效果。水凝胶疫苗可显着促进引流淋巴结和肿瘤浸润性T淋巴细胞中CD8 ⁺ T细胞的产生。这些发现表明，通过用抗原和免疫戊内酯包封的可注射多肽水凝胶对DC的体内程序能够指导针对癌症的免疫反应。我们的研究还暗示，这种水凝胶可以充当疫苗的多功能递送平台。