Sa2025 Etrolizumab-Mediated Ex Vivo Modulation of Beta7 Cell Surface Receptors in Nonhuman Primate and Human Peripheral Blood Supports the Proposed Mechanism of Action

Pharmacology of AMG 181, a human anti‐α4β7 antibody that specifically alters trafficking of gut‐homing T cells

“…The AMG 181 effects on various T cell count elevations in cynomolgus monkeys (Pan et al ., 2012a) were not observed in healthy volunteers (single dose of 0.7 mg s.c. to 420 mg i.v.) (Pan et al ., 2012b), consistent with the results reported for vedolizumab (Feagan et al ., 2005; 2008; Fedyk et al ., ) and etrolizumab (Stefanich et al ., ; Rutgeerts et al ., ; Williams et al ., ). A plausible explanation is that down‐modulation of target cell surface receptors occurred in humans but not in cynomolgus monkeys (Williams et al ., ).…”

“…(Pan et al ., 2012b), consistent with the results reported for vedolizumab (Feagan et al ., 2005; 2008; Fedyk et al ., ) and etrolizumab (Stefanich et al ., ; Rutgeerts et al ., ; Williams et al ., ). A plausible explanation is that down‐modulation of target cell surface receptors occurred in humans but not in cynomolgus monkeys (Williams et al ., ). In ex vivo studies using human peripheral blood, vedolizumab and etrolizumab led to ∼50 and ∼60–70% receptor internalization respectively (Williams et al ., ; Yang et al ., ).…”

“…A plausible explanation is that down‐modulation of target cell surface receptors occurred in humans but not in cynomolgus monkeys (Williams et al ., ). In ex vivo studies using human peripheral blood, vedolizumab and etrolizumab led to ∼50 and ∼60–70% receptor internalization respectively (Williams et al ., ; Yang et al ., ). An exception to these results is the observed CD4+ CM cell increases in both cynomolgus monkeys (Pullen et al ., ) and subjects with CD (Vermeire et al ., ) under PF‐00547659 treatment.…”