Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.
Journal
Nature nanotechnology
ISSN: 1748-3395
Titre abrégé: Nat Nanotechnol
Pays: England
ID NLM: 101283273
Informations de publication
Date de publication:
15 Mar 2024
15 Mar 2024
Historique:
received:
19
12
2022
accepted:
18
01
2024
medline:
16
3
2024
pubmed:
16
3
2024
entrez:
16
3
2024
Statut:
aheadofprint
Résumé
Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory. Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines.
Identifiants
pubmed: 38491184
doi: 10.1038/s41565-024-01615-3
pii: 10.1038/s41565-024-01615-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : CA244726-01
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : CA244726-01
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : CA244726-01
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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