STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity
<jats:title>Abstract</jats:title><jats:p>Activation 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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/147842 |
| _version_ | 1826217364615593984 |
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| author | Dane, Eric L Belessiotis-Richards, Alexis Backlund, Coralie Wang, Jianing Hidaka, Kousuke Milling, Lauren E Bhagchandani, Sachin Melo, Mariane B Wu, Shengwei Li, Na Donahue, Nathan Ni, Kaiyuan Ma, Leyuan Okaniwa, Masanori Stevens, Molly M Alexander-Katz, Alfredo Irvine, Darrell J |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Dane, Eric L Belessiotis-Richards, Alexis Backlund, Coralie Wang, Jianing Hidaka, Kousuke Milling, Lauren E Bhagchandani, Sachin Melo, Mariane B Wu, Shengwei Li, Na Donahue, Nathan Ni, Kaiyuan Ma, Leyuan Okaniwa, Masanori Stevens, Molly M Alexander-Katz, Alfredo Irvine, Darrell J |
| author_sort | Dane, Eric L |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Activation 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.</jats:p> |
| first_indexed | 2024-09-23T17:02:50Z |
| format | Article |
| id | mit-1721.1/147842 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:02:50Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1478422024-01-29T21:55:29Z STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity Dane, Eric L Belessiotis-Richards, Alexis Backlund, Coralie Wang, Jianing Hidaka, Kousuke Milling, Lauren E Bhagchandani, Sachin Melo, Mariane B Wu, Shengwei Li, Na Donahue, Nathan Ni, Kaiyuan Ma, Leyuan Okaniwa, Masanori Stevens, Molly M Alexander-Katz, Alfredo Irvine, Darrell J 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 <jats:title>Abstract</jats:title><jats:p>Activation 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.</jats:p> 2023-02-01T18:20:09Z 2023-02-01T18:20:09Z 2022 2023-02-01T18:16:10Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147842 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). en 10.1038/S41563-022-01251-Z Nature Materials Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Dane, Eric L Belessiotis-Richards, Alexis Backlund, Coralie Wang, Jianing Hidaka, Kousuke Milling, Lauren E Bhagchandani, Sachin Melo, Mariane B Wu, Shengwei Li, Na Donahue, Nathan Ni, Kaiyuan Ma, Leyuan Okaniwa, Masanori Stevens, Molly M Alexander-Katz, Alfredo Irvine, Darrell J STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity |
| title | STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity |
| title_full | STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity |
| title_fullStr | STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity |
| title_full_unstemmed | STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity |
| title_short | STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity |
| title_sort | sting agonist delivery by tumour penetrating peg lipid nanodiscs primes robust anticancer immunity |
| url | https://hdl.handle.net/1721.1/147842 |
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