Nanshan School, Guangzhou Medical University, Guangzhou, 510810, China.
Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Biomater Sci. 2022 Mar 2;10(5):1352-1363. doi: 10.1039/d1bm01596f.
Tumor recurrence and metastasis have become thorny problems in clinical tumor therapy. Vaccine-mediated antitumor immune response has emerged as a significant postoperative inhibition for tumor recurrence and metastasis. However, limited tumor antigens are not conducive to trigger complete antigen-specific T cell-mediated immune responses. Herein, the design of a hydrogel vaccine system containing a granulocyte-macrophage colony stimulating factor (GM-CSF), based on surgically removed tumor cell lysates, was reported. The hydrogel was formed by crosslinking tumor cell lysates and alginate at low temperatures. The GM-CSF was released from the hydrogel to recruit dendritic cells (DCs), which provided a completely personalized tumor antigen pool. They were combined to foster the production of powerful antigen-specific T cells. The personalized hydrogel was implanted at the surgical site and it stimulated the antitumor immune response for the inhibition of residual tumor cells. Delightfully, the personalized hydrogel inhibited the tumor recurrence and metastasis well in a post-surgical mice tumor model, in combination with a programmed death-ligand 1 antibody (αPD-L1). The results demonstrated that the development of a personalized hydrogel and a combination of αPD-L1 provided a new strategy to prevent tumor recurrence and metastasis.
肿瘤复发和转移已成为临床肿瘤治疗中的棘手问题。疫苗介导的抗肿瘤免疫反应已成为抑制肿瘤复发和转移的重要术后手段。然而，有限的肿瘤抗原不利于触发完全的抗原特异性 T 细胞介导的免疫反应。在此，报告了一种基于手术切除的肿瘤细胞裂解物的含有粒细胞-巨噬细胞集落刺激因子（GM-CSF）的水凝胶疫苗系统的设计。该水凝胶通过在低温下交联肿瘤细胞裂解物和藻酸盐形成。GM-CSF 从水凝胶中释放出来招募树突状细胞（DCs），为其提供完全个性化的肿瘤抗原库。它们结合在一起，促进产生强大的抗原特异性 T 细胞。个性化水凝胶被植入手术部位，刺激抗肿瘤免疫反应，抑制残留肿瘤细胞。令人高兴的是，个性化水凝胶与程序性死亡配体 1 抗体（αPD-L1）联合使用，可很好地抑制术后小鼠肿瘤模型中的肿瘤复发和转移。结果表明，个性化水凝胶的开发和 αPD-L1 的联合应用为预防肿瘤复发和转移提供了一种新策略。
