Etrolizumab (rhuMAb Beta7) is a gut-selective, anti-β7 integrin monoclonal antibody. Etrolizumab is specific targeting of the β7 subunit of α4β7 and αEβ7 integrins with Ki values of 18 nM and 1800 pM for Human α4β7 and Human αEβ7-293, respectively. Etrolizumab can be used in research of inflammatory bowel disease (IBD)[1][2].
Etrolizumab (rhuMAb Beta7) binds the β7 subunit of both α4β7 and αEβ7 integrins with high affinity, with Kd values of 18 nM, 1800 pM, 181 pM, 116 pM, 57 pM, 31.7 pM, and 25.7 pM for Human α4β7, Human αEβ7-293, Mouse α4β7-38C13, Human α4β7-293, Rabbit PBLs, Human PBLs, and Cyno PBLs, respectively[1].
Etrolizumab (RPMI 8866 cells and αEβ7-293 cells) blocks the interaction of α4β7 with its cognate ligands MAdCAM-1 and VCAM-1 with IC50 values of 0.075 and 0.089 nM, respectively, and blocks the interaction between αEβ7 and its ligand E-cadherin with an IC50 value of 3.96 nM[1].
Etrolizumab (rhuMAb Beta7; 5 mg/kg; i.v.; once; normal female BALB/c mice) decreases β7 integrins on T lymphocytes[2].
Etrolizumab (200 µg (100 µL); i.p.; once) inhibits lymphocyte homing in the CD45RBhigh T cell-reconstituted SCID mouse model of colitis[2].
| Animal Model: | Normal female BALB/c mice (17-21 g)[2] |
| Dosage: | 5 mg/kg |
| Administration: | Intravenous injection; once |
| Result: | Had 98.3% of intraepithelial CD8+ T-cell β7 integrin receptors and 90.0% of intraepithelial CD4+ T-cell β7 integrin receptors after 24 h. |
| Animal Model: | SCID mouse model of colitis[2] |
| Dosage: | 200 µg (100 µL) |
| Administration: | Intraperitoneal injection; once |
| Result: | Blocked lymphocyte recruitment and homing to the inflamed colon. |
[1]. Tang MT, et, al. Review article: nonclinical and clinical pharmacology, pharmacokinetics and pharmacodynamics of etrolizumab, an anti-β7 integrin therapy for inflammatory bowel disease. Aliment Pharmacol Ther. 2018 Jun;47(11):1440-1452.
[2]. Stefanich EG, et, al. A humanized monoclonal antibody targeting the β7 integrin selectively blocks intestinal homing of T lymphocytes. Br J Pharmacol. 2011 Apr;162(8):1855-70.