含氟聚合物
免疫疗法
医学
癌症研究
癌症
癌症免疫疗法
抗原
转移
免疫系统
卵清蛋白
树突状细胞
免疫检查点
免疫学
内科学
化学
有机化学
聚合物
作者
Jun Xu,Jia Lv,Qi Zhuang,Zongjin Yang,Zhiqin Cao,Ligeng Xu,Pei Pei,Chao Wang,Hanfei Wu,Ziliang Dong,Yu Chao,Chao Wang,Kai Yang,Rui Peng,Yiyun Cheng,Zhuang Liu
标识
DOI:10.1038/s41565-020-00781-4
摘要
Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate personalized nanovaccines based on a cationic fluoropolymer for post-surgical cancer immunotherapy. Nanoparticles formed by mixing the fluoropolymer with a model antigen ovalbumin, induce dendritic cell maturation via the Toll-like receptor 4 (TLR4)-mediated signalling pathway, and promote antigen transportation into the cytosol of dendritic cells, which leads to an effective antigen cross-presentation. Such a nanovaccine inhibits established ovalbumin-expressing B16-OVA melanoma. More importantly, a mix of the fluoropolymer with cell membranes from resected autologous primary tumours synergizes with checkpoint blockade therapy to inhibit post-surgical tumour recurrence and metastases in two subcutaneous tumour models and an orthotopic breast cancer tumour. Furthermore, in the orthotopic tumour model, we observed a strong immune memory against tumour rechallenge. Our work offers a simple and general strategy for the preparation of personalized cancer vaccines to prevent post-operative cancer recurrence and metastasis. A fluoropolymer-based cancer nanovaccine that delivers antigens directly to the cytosol of dendritic cells and elicits strong antitumour immune responses inhibiting tumour growth in animal models can be used to produce personalized treatment for post-surgical immunotherapy.
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