TY - JOUR
T1 - A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy
AU - Xu, Jun
AU - Lv, Jia
AU - Zhuang, Qi
AU - Yang, Zongjin
AU - Cao, Zhiqin
AU - Xu, Ligeng
AU - Pei, Pei
AU - Wang, Chenya
AU - Wu, Hanfei
AU - Dong, Ziliang
AU - Chao, Yu
AU - Wang, Chao
AU - Yang, Kai
AU - Peng, Rui
AU - Cheng, Yiyun
AU - Liu, Zhuang
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85094978293
U2 - 10.1038/s41565-020-00781-4
DO - 10.1038/s41565-020-00781-4
M3 - 文章
C2 - 33139933
AN - SCOPUS:85094978293
SN - 1748-3387
VL - 15
SP - 1043
EP - 1052
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 12
ER -