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Differential effects of ontamalimab versus vedolizumab on immune cell trafficking in intestinal inflammation and IBD

ABSTRACT: Differential effects of ontamalimab versus vedolizumab on immune cell trafficking in intestinal inflammation and IBD

PROVIDER: PRJNA957308 | ENA |

REPOSITORIES: ENA

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Differential effects of ontamalimab versus vedolizumab on immune cell trafficking in intestinal inflammation and IBD

Project description:The anti-MAdCAM-1 antibody ontamalimab demonstrated efficacy in a phase II trial in UC and results of early terminated phase III trials are pending, but its precise mechanisms of action are still unclear. Thus, we explored the mechanisms of ontamalimab and compared it to the anti-α4β7 antibody vedolizumab.

2023-06-05 | GSE230059 | GEO

Transcriptional behavior of regulatory T cells predicts IBD patient responses to vedolizumab therapy

Project description:Vedolizumab (VDZ) is used to treat patients with IBD but the exact way it works is not known. We studied the immune system in the blood and intestine of patients treated with VDZ and found immune characteristics that correlated with response.

2022-08-23 | GSE184593 | GEO

Predicting response to vedolizumab therapy using mucosal transcriptomics in IBD patients

Project description:In this study we wanted to identify baseline predictors of successful vedolizumab therapy in patients with inflammatory bowel disease.

2019-08-23 | E-MTAB-7845 | biostudies-arrayexpress

Predicting response to vedolizumab therapy using mucosal transcriptomics in IBD patients

Project description:Predicting response to vedolizumab therapy using mucosal transcriptomics in IBD patients

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Responsiveness to vedolizumab therapy in ulcerative colitis is associated with alterations in immune cell-cell communications

Project description:Ulcerative colitis (UC) is a major subtype of inflammatory bowel disease (IBD), a spectrum of chronic intestinal disorders caused by dysregulated immune responses to gut microbiota. Although transcriptional and functional changes in a number of immune cell types have been implicated in the pathogenesis of IBD, the cellular interactions and signals that drive these changes have been less well-studied. Moreover, the precise mechanisms of action underlying many biologic therapies, including the anti-47 integrin antagonist vedolizumab, remain incompletely understood. Our study aimed to explore possible additional mechanisms through which vedolizumab acts.

2023-06-15 | GSE228165 | GEO

Transcriptional behavior of regulatory T cells predicts IBD patient responses to vedolizumab therapy

Project description:Transcriptional behavior of regulatory T cells predicts IBD patient responses to vedolizumab therapy

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Vedolizumab efficacy is associated with decreased intracolonic dendritic cells, not memory T cells [P444]

Project description:Background: Vedolizumab, an antibody blocking integrin α4β7, is a safe and effective therapy for Crohn’s disease and ulcerative colitis. Blocking α4β7 from binding its cognate addressin MAdCAM-1 on intestinal blood vessel endothelial cells prevents T cells from migrating to the gut mucosa in animal models. However, data supporting this mechanism of action in humans is limited. Methods: We conducted a cross-sectional case-control study to evaluate the effect of vedolizumab on intestinal immune cell populations while avoiding the confounding effect resolving inflammation could have on the cellularity of the colonic mucosa in treatment-responsive patients. Colon biopsies from 71 case patients receiving vedolizumab were matched with biopsies from 71 control patients, similar in disease type, medications, anatomic location, and inflammation. Biopsies were analyzed by flow cytometry and full mRNA transcriptome sequencing of sorted T cells. Results: No difference was seen between vedolizumab recipients and controls in the quantity of any antigen-experienced lymphocyte subset, nor the quality of the transcriptome in any experienced T cell subset. Fewer naïve colonic B and T cells were seen in vedolizumab recipients than controls, regardless of response. The only immune population that was significantly reduced exclusively in the colonic mucosa of vedolizumab-responsive patients was CD1c+ (BDCA1+) dendritic cells. In blood, these dendritic cells ubiquitously express more α4β7 per cell than almost any other circulating leukocyte, but rapidly downregulate α4β7 expression upon vedolizumab exposure. Conclusions: The clinical efficacy of vedolizumab thus reveals integrin α4β7-dependent dendritic cell migration to the intestinal mucosa to be central to IBD pathogenesis.

2023-08-01 | GSE234981 | GEO

Vedolizumab efficacy is associated with decreased intracolonic dendritic cells, not memory T cells [P430]

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Residual homing of a α4β7-expressing β1+PI16+ regulatory T cell subset correlates with exposure-efficacy of vedolizumab

Project description:In vitro and in vivo data from our lab show that TReg cells exhibit a right-shifted vedolizumab binding profile compared with TEff cells. Consistently, in a certain concentration range, the residual adhesion, transmigration and homing of TReg cells was higher than that of TEff cells. To better understand why vedolizumab binding was different between TReg and TEff in a certain concentration range, we performed single cell RNA sequencing of Memory CD4 T cells expressing α4 and β7 integrin and compared cells binding to vedolizumab or not binding to vedolizumab (previously purified using FACS with fluorescently labelled vedolizumab).

2021-09-10 | GSE162624 | GEO

Unravelling the mechanism of action of Tofacitinib on immune cell trafficking through IBD-associated microvasculature

Project description:Unravelling the mechanism of action of Tofacitinib on immune cell trafficking through IBD-associated microvasculature

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