A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy
Jun Xu,1 Jia Lv,2 Qi Zhuang,1 Zongjin Yang,1 Zhiqin Cao,1 Ligeng Xu,1 Pei Pei,3 Chenya Wang,1 Hanfei Wu,1 Ziliang Dong,1 Yu Chao,1 Chao Wang ,1 Kai Yang,3 Rui Peng,1,* Yiyun Cheng 4,2,* and Zhuang Liu 1,*
1Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, China.
2South China Advanced Institute for Soft Matter Science and Technology, South China University of Technology, Guangzhou, China.
3State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.
4Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
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.