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Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination

ABSTRACT: Multivalent presentation of ligands often enhances receptor activation and downstream signaling. DNA origami offers 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 spacing of CpG oligonucleotides. CpG engages Toll-like receptors and thereby acts to activate dendritic cells. Through in vitro cell-culture studies and in vivo tumor-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 synergizes effectively 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE251850 | GEO | 2024/02/01

REPOSITORIES: GEO

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