FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3196804847> ?p ?o ?g. }

• W3196804847 endingPage "1566" @default.
• W3196804847 startingPage "1551" @default.
• W3196804847 abstract "The anti-α4β7 integrin antibody vedolizumab is administered at a fixed dose for the treatment of IBDs. This leads to a wide range of serum concentrations in patients and previous studies had suggested that highest exposure levels are associated with suboptimal clinical response. We aimed to determine the mechanisms underlying these non-linear exposure-efficacy characteristics of vedolizumab.We characterised over 500 samples from more than 300 subjects. We studied the binding of vedolizumab to T cells and investigated the functional consequences for dynamic adhesion, transmigration, gut homing and free binding sites in vivo. Employing single-cell RNA sequencing, we characterised α4β7 integrin-expressing T cell populations 'resistant' to vedolizumab and validated our findings in vitro and in samples from vedolizumab-treated patients with IBD. We also correlated our findings with a post-hoc analysis of the Gemini II and III studies.Regulatory T (TReg) cells exhibited a right-shifted vedolizumab binding profile compared with effector T (TEff) cells. Consistently, in a certain concentration range, the residual adhesion, transmigration, homing of and availability of functional α4β7 on TReg cells in vivo was higher than that of/on TEff cells. We identified a vedolizumab-'resistant' α4β7-expressing β1+PI16+ TReg cell subset with pronounced regulatory properties as the substrate for this effect. Our observations correlated with exposure-efficacy data from Gemini II and III trials.Completely blocking TEff cell trafficking with vedolizumab, while simultaneously permitting residual homing of powerful TReg cells in an optimal 'therapeutic window' based on target exposure levels might be a strategy to optimise treatment outcomes in patients with IBD." @default.
• W3196804847 created "2021-09-13" @default.
• W3196804847 creator A5004377423 @default.
• W3196804847 creator A5017444688 @default.
• W3196804847 creator A5020753617 @default.
• W3196804847 creator A5027340443 @default.
• W3196804847 creator A5029918239 @default.
• W3196804847 creator A5032480207 @default.
• W3196804847 creator A5034003178 @default.
• W3196804847 creator A5044794339 @default.
• W3196804847 creator A5044952697 @default.
• W3196804847 creator A5049365446 @default.
• W3196804847 creator A5059225038 @default.
• W3196804847 creator A5062492061 @default.
• W3196804847 creator A5065672260 @default.
• W3196804847 creator A5067562114 @default.
• W3196804847 creator A5085014592 @default.
• W3196804847 date "2021-08-30" @default.
• W3196804847 modified "2023-10-14" @default.
• W3196804847 title "Residual homing of α4β7-expressing β1⁺PI16⁺ regulatory T cells with potent suppressive activity correlates with exposure-efficacy of vedolizumab" @default.
• W3196804847 cites W1940516511 @default.
• W3196804847 cites W1944355477 @default.
• W3196804847 cites W1993907368 @default.
• W3196804847 cites W2000069945 @default.
• W3196804847 cites W2004608617 @default.
• W3196804847 cites W2023078169 @default.
• W3196804847 cites W2029863800 @default.
• W3196804847 cites W2035809865 @default.
• W3196804847 cites W2077531651 @default.
• W3196804847 cites W2119160928 @default.
• W3196804847 cites W2126261790 @default.
• W3196804847 cites W2142171084 @default.
• W3196804847 cites W2143758098 @default.
• W3196804847 cites W2162805528 @default.
• W3196804847 cites W2165290386 @default.
• W3196804847 cites W2328126238 @default.
• W3196804847 cites W2414026316 @default.
• W3196804847 cites W2583464358 @default.
• W3196804847 cites W2586374020 @default.
• W3196804847 cites W2615644319 @default.
• W3196804847 cites W2623221337 @default.
• W3196804847 cites W2773289068 @default.
• W3196804847 cites W2791118194 @default.
• W3196804847 cites W2792406291 @default.
• W3196804847 cites W2799380236 @default.
• W3196804847 cites W2800832402 @default.
• W3196804847 cites W2801753207 @default.
• W3196804847 cites W2803719252 @default.
• W3196804847 cites W2808336191 @default.
• W3196804847 cites W2888701558 @default.
• W3196804847 cites W2911819327 @default.
• W3196804847 cites W2912982848 @default.
• W3196804847 cites W2913111141 @default.
• W3196804847 cites W2919105977 @default.
• W3196804847 cites W2945386610 @default.
• W3196804847 cites W2946468288 @default.
• W3196804847 cites W2947144073 @default.
• W3196804847 cites W2949971221 @default.
• W3196804847 cites W2970843227 @default.
• W3196804847 cites W3085772379 @default.
• W3196804847 cites W4211241312 @default.
• W3196804847 cites W4296224660 @default.
• W3196804847 doi "https://doi.org/10.1136/gutjnl-2021-324868" @default.
• W3196804847 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34462337" @default.
• W3196804847 hasPublicationYear "2021" @default.
• W3196804847 type Work @default.
• W3196804847 sameAs 3196804847 @default.
• W3196804847 citedByCount "17" @default.
• W3196804847 countsByYear W31968048472021 @default.
• W3196804847 countsByYear W31968048472022 @default.
• W3196804847 countsByYear W31968048472023 @default.
• W3196804847 crossrefType "journal-article" @default.
• W3196804847 hasAuthorship W3196804847A5004377423 @default.
• W3196804847 hasAuthorship W3196804847A5017444688 @default.
• W3196804847 hasAuthorship W3196804847A5020753617 @default.
• W3196804847 hasAuthorship W3196804847A5027340443 @default.
• W3196804847 hasAuthorship W3196804847A5029918239 @default.
• W3196804847 hasAuthorship W3196804847A5032480207 @default.
• W3196804847 hasAuthorship W3196804847A5034003178 @default.
• W3196804847 hasAuthorship W3196804847A5044794339 @default.
• W3196804847 hasAuthorship W3196804847A5044952697 @default.
• W3196804847 hasAuthorship W3196804847A5049365446 @default.
• W3196804847 hasAuthorship W3196804847A5059225038 @default.
• W3196804847 hasAuthorship W3196804847A5062492061 @default.
• W3196804847 hasAuthorship W3196804847A5065672260 @default.
• W3196804847 hasAuthorship W3196804847A5067562114 @default.
• W3196804847 hasAuthorship W3196804847A5085014592 @default.
• W3196804847 hasConcept C126322002 @default.
• W3196804847 hasConcept C151872237 @default.
• W3196804847 hasConcept C153911025 @default.
• W3196804847 hasConcept C185592680 @default.
• W3196804847 hasConcept C18903297 @default.
• W3196804847 hasConcept C202751555 @default.
• W3196804847 hasConcept C203014093 @default.
• W3196804847 hasConcept C207001950 @default.
• W3196804847 hasConcept C2776207728 @default.
• W3196804847 hasConcept C2778260677 @default.
• W3196804847 hasConcept C2779134260 @default.

• next