학술논문
Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination
Document Type
Article
Author
Zeng, Yang C.; Young, Olivia J.; Wintersinger, Christopher M.; Anastassacos, Frances M.; MacDonald, James I.; Isinelli, Giorgia; Dellacherie, Maxence O.; Sobral, Miguel; Bai, Haiqing; Graveline, Amanda R.; Vernet, Andyna; Sanchez, Melinda; Mulligan, Kathleen; Choi, Youngjin; Ferrante, Thomas C.; Keskin, Derin B.; Fell, Geoffrey G.; Neuberg, Donna; Wu, Catherine J.; Mooney, David J.; Kwon, Ick Chan; Ryu, Ju Hee; Shih, William M.
Source
Nature Nanotechnology; 20240101, Issue: Preprints p1-11, 11p
Subject
Language
ISSN
17483387; 17483395
Abstract
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.