STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity
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s41563-022-01251-z.pdf
Description
Published version
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16.71 MB
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Checksum (MD5)
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Author(s)
Dane, Eric L
Belessiotis-Richards, Alexis
Backlund, Coralie
Wang, Jianing
Hidaka, Kousuke
Milling, Lauren E
Bhagchandani, Sachin
Melo, Mariane B
Wu, Shengwei
Li, Na
Date Issued
2022
Journal
Nature Materials
Publisher
Springer Science and Business Media LLC
Citation
Dane, Eric L, Belessiotis-Richards, Alexis, Backlund, Coralie, Wang, Jianing, Hidaka, Kousuke et al. 2022. "STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity." Nature Materials, 21 (6).
Version
Final published version
Abstract
AbstractActivation of the innate immune STimulator of INterferon Genes (STING) pathway potentiates antitumour immunity, but systemic delivery of STING agonists to tumours is challenging. We conjugated STING-activating cyclic dinucleotides (CDNs) to PEGylated lipids (CDN-PEG-lipids; PEG, polyethylene glycol) via a cleavable linker and incorporated them into lipid nanodiscs (LNDs), which are discoid nanoparticles formed by self-assembly. Compared to state-of-the-art liposomes, intravenously administered LNDs carrying CDN-PEG-lipid (LND-CDNs) exhibited more efficient penetration of tumours, exposing the majority of tumour cells to STING agonist. A single dose of LND-CDNs induced rejection of established tumours, coincident with immune memory against tumour rechallenge. Although CDNs were not directly tumoricidal, LND-CDN uptake by cancer cells correlated with robust T-cell activation by promoting CDN and tumour antigen co-localization in dendritic cells. LNDs thus appear promising as a vehicle for robust delivery of compounds throughout solid tumours, which can be exploited for enhanced immunotherapy.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Ragon Institute of MGH, MIT and Harvard
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41563-022-01251-Z
