Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, China.
South China Advanced Institute for Soft Matter Science and Technology, South China University of Technology, Guangzhou, China.
Nat Nanotechnol. 2020 Dec;15(12):1043-1052. doi: 10.1038/s41565-020-00781-4. Epub 2020 Nov 2.
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.
癌症手术后转移和复发仍然是治疗失败的一个重要原因。在这里,我们展示了一种基于阳离子氟聚合物的个性化纳米疫苗的通用制造策略,用于手术后癌症免疫治疗。通过将氟聚合物与模型抗原卵清蛋白混合形成的纳米颗粒,通过 Toll 样受体 4(TLR4)介导的信号通路诱导树突状细胞成熟,并促进抗原进入树突状细胞的细胞质,从而有效进行抗原交叉呈递。这种纳米疫苗抑制了已建立的表达卵清蛋白的 B16-OVA 黑色素瘤。更重要的是,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治疗协同作用,抑制两种皮下肿瘤模型和原位乳腺癌肿瘤的手术后肿瘤复发和转移。此外,在原位肿瘤模型中,我们观察到对肿瘤再挑战的强烈免疫记忆。我们的工作为制备个性化癌症疫苗以预防术后癌症复发和转移提供了一种简单而通用的策略。