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Nat Nanotechnol ; 15(12): 1043-1052, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33139933

RESUMO

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.


Assuntos
Vacinas Anticâncer/uso terapêutico , Polímeros de Fluorcarboneto/uso terapêutico , Melanoma Experimental/prevenção & controle , Nanopartículas/uso terapêutico , Animais , Vacinas Anticâncer/química , Células Cultivadas , Feminino , Polímeros de Fluorcarboneto/química , Imunoterapia , Melanoma Experimental/imunologia , Melanoma Experimental/cirurgia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/química , Ovalbumina/uso terapêutico , Polietilenoimina/química , Polietilenoimina/uso terapêutico
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