Etrolizumab-s Does Not Induce Residual Trafficking of Regulatory T Cells

Schweda A, Becker E, Wiendl M, Atreya R, Atreya I, Müller T, Neurath M, Zundler S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Abstract

Background

Blocking immune cell gut homing via α4β7 integrin with the monoclonal antibody vedolizumab is an established therapeutic strategy in inflammatory bowel disease. However, despite promising preclinical and phase 2 clinical data, the anti-β7 antibody etrolizumab yielded disappointing results in a large phase 3 trial program in UC. Mechanistic explanations are still lacking. We have recently shown that vedolizumab is associated with residual homing of regulatory T (Treg) cells in a certain exposure range and aimed to investigate whether a similar mechanism applies for etrolizumab.

Methods

We used flow cytometry, competitive dynamic adhesion, and transmigration assays to assess binding of the etrolizumab surrogate (etrolizumab-s) antibody FIB504 to Treg and effector T cells (Teff) and to explore the impact on cell trafficking.

Results

We observed only minimal differences in the binding of etrolizumab-s to Treg and Teff cells. Dynamic adhesion and transmigration of Treg and Teff cells was not substantially differentially affected at relevant concentrations. The β1+ and PI16+ Treg cells were only resistant to etrolizumab-s at low concentrations.

Conclusions

Etrolizumab does not seem to induce notable residual trafficking of Treg cells. Thus, the Teff overweight in the inflamed gut might persist despite reduced overall T cell recruitment. This might be one piece of the puzzle to explain recent clinical results in phase 3.

Authors with CRIS profile

Emily Becker Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Maximilian Wiendl Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Imke Atreya Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Tanja Müller Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

How to cite

APA:

Schweda, A., Becker, E., Wiendl, M., Atreya, R., Atreya, I., Müller, T.,... Zundler, S. (2022). Etrolizumab-s Does Not Induce Residual Trafficking of Regulatory T Cells. Inflammatory Bowel Diseases. https://doi.org/10.1093/ibd/izac137

MLA:

Schweda, Anna, et al. "Etrolizumab-s Does Not Induce Residual Trafficking of Regulatory T Cells." Inflammatory Bowel Diseases (2022).

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