Etrolizumab-s Does Not Induce Residual Trafficking of Regulatory T Cells.
Inflamm Bowel Dis
; 28(11): 1746-1755, 2022 11 02.
Article
em En
| MEDLINE
| ID: mdl-35815779
ABSTRACT
BACKGROUND:
Blocking immune cell gut homing via α4ß7 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-ß7 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 ß1+ 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.
The efficacy of etrolizumab in phase 3 was disappointing. Our data suggest that, unlike vedolizumab, etrolizumab does not induce relevant residual trafficking of regulatory T cells. This might be one part of the explanation for recent observations in clinical trials.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
/
Colite Ulcerativa
Limite:
Humans
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha