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A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy
Nature Nanotechnology ( IF 38.1 ) Pub Date : 2020-11-02 , DOI: 10.1038/s41565-020-00781-4
Jun Xu , Jia Lv , Qi Zhuang , Zongjin Yang , Zhiqin Cao , Ligeng Xu , Pei Pei , Chenya Wang , Hanfei Wu , Ziliang Dong , Yu Chao , Chao Wang , Kai Yang , Rui Peng , Yiyun Cheng , Zhuang Liu

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.



中文翻译:

基于含氟聚合物的个性化纳米疫苗的一般策略用于手术后癌症免疫治疗

手术切除后的癌转移和复发仍然是治疗失败的重要原因。在这里,我们展示了一种基于阳离子含氟聚合物的个性化纳米疫苗的一般策略,用于手术后癌症免疫治疗。含氟聚合物与模型抗原卵清蛋白混合后形成的纳米颗粒,通过Toll样受体4(TLR4)介导的信号传导途径诱导树突状细胞成熟,并促进抗原转运到树突状细胞的胞质溶胶中,从而导致有效的抗原交叉介绍。这样的纳米疫苗抑制已建立的表达卵白蛋白的B16-OVA黑色素瘤。更重要的是,含氟聚合物与切除的自体原发性肿瘤细胞膜的混合物与检查点阻断疗法协同作用,以抑制两种皮下肿瘤模型和原位乳腺癌肿瘤中的术后肿瘤复发和转移。此外,在原位肿瘤模型中,我们观察到了针对肿瘤再发的强大免疫记忆。我们的工作为制备个性化的癌症疫苗提供了简单而通用的策略,以预防术后癌症的复发和转移。

更新日期:2020-11-02
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