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231226s2024 xx |||||o 00| ||eng c |
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|a 10.1002/adma.202309039
|2 doi
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|a pubmed25n1212.xml
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|a DE-627
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|e rakwb
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|a eng
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| 100 |
1 |
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|a Shin, Hong Sik
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Molecular Masking of Synthetic Immunomodulator Evokes Antitumor Immunity With Reduced Immune Tolerance and Systemic Toxicity by Temporal Activity Recovery and Sustained Stimulation
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|c 2024
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 04.03.2024
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|a Date Revised 04.03.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2023 Wiley-VCH GmbH.
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|a Activation of the innate immune system counteracts tumor-induced immunosuppression. Hence, small molecule-based toll-like receptor 7/8 agonists (TLR7/8a), which can modulate immunosuppression in the tumor microenvironment along with the activation of innate immunity, are emerging as essential components of cancer immunotherapy. However, the clinical application of synthetic TLR7/8a therapies is limited by systemic immune-associated toxicity and immune tolerance induced by uncontrolled stimulatory activities and repeated treatments. To address these limitations, a dynamic immunomodulation strategy incorporating masking and temporal recovery of the activity of TLR7/8a through prodrug-like TLR7/8a (pro-TLR7/8a) at the molecular level and a sustained and controlled release of active TLR7/8a from nanoliposome (pro-TLR7/8a) (NL(pro-TLR7/8)) in a macroscale depot are designed. Immunization with cationic NL(pro-TLR7/8) and anionic antigens triggers robust activation of innate immune cells as well as antigen-specific T cell responses, eliciting reprogramming of immunosuppressive cells into tumor-suppressive cells, with decreased systemic adverse effects and immune tolerance. Combination treatment with NL(pro-TLR7/8a) and immune checkpoint inhibitors (anti-CTLA-4 plus anti-PD-L1) or nanoliposomes (Doxorubicin) has synergistic effects on antitumor immunity in various tumor models. The concept of pro-TLR7/8a suggested herein may facilitate the advancement of small-molecule-based immunomodulators for clinical translation and safe and effective cancer immunotherapy
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| 650 |
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|a Journal Article
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| 650 |
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|a cancer immunotherapy
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| 650 |
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4 |
|a immune checkpoint inhibitors
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| 650 |
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4 |
|a immune stimulation
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| 650 |
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4 |
|a immune tolerance
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| 650 |
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4 |
|a immunosuppression
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| 650 |
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4 |
|a toll-like receptor agonist
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| 650 |
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7 |
|a Toll-Like Receptor 7
|2 NLM
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| 650 |
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7 |
|a Immunologic Factors
|2 NLM
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| 650 |
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7 |
|a Adjuvants, Immunologic
|2 NLM
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| 700 |
1 |
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|a Kim, Sohyun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Jin, Seung Mo
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yoo, Yeon Jeong
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Heo, Jang Hun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Lim, Yong Taik
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g 36(2024), 9 vom: 10. März, Seite e2309039
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnas
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| 773 |
1 |
8 |
|g volume:36
|g year:2024
|g number:9
|g day:10
|g month:03
|g pages:e2309039
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| 856 |
4 |
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|u http://dx.doi.org/10.1002/adma.202309039
|3 Volltext
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