etrolizumab

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Ligands
etrolizumab

GtoPdb Ligand ID: 8407

Synonyms: PRO145223 | RG-7413 | RG7413 | rhuMAb Beta7

Comment: Etrolizumab is a humanized monoclonal antibody targeting integrin receptors containing the ITGB7 (β7) subunit (namely α4β7 and αEβ7).
Peptide sequence information for this antibody is available from its IMGT/mAb-DB record. Peptide sequence matches indicate that US7528236 is the covering patent [4]. The likely candidate antibody clone is that designated hu504.32R.
Etrolizumab has a slightly different mechanism of action compared to the already approved ulcerative colitis biologic vedolizumab (Entyvio®), which targets only α4β7 integrin.

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References
1. Cepek KL, Parker CM, Madara JL, Brenner MB. (1993) Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells. J Immunol, 150 (8 Pt 1): 3459-70. [PMID:8468482]
2. Feagan BG, Greenberg GR, Wild G, Fedorak RN, Paré P, McDonald JW, Dubé R, Cohen A, Steinhart AH, Landau S et al.. (2005) Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med, 352 (24): 2499-507. [PMID:15958805]
3. Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S et al.. (2013) Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med, 369 (8): 699-710. [PMID:23964932]
4. Fong S, Dennis MS. (2009) Humanized anti-beta7 antagonists and uses therefor. Patent number: US7528236 B2. Assignee: Genentech, Inc.. Priority date: 03/09/2004. Publication date: 09/05/2009.
5. Holzmann B, McIntyre BW, Weissman IL. (1989) Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell, 56 (1): 37-46. [PMID:2463092]
6. Hu MC, Crowe DT, Weissman IL, Holzmann B. (1992) Cloning and expression of mouse integrin beta p(beta 7): a functional role in Peyer's patch-specific lymphocyte homing. Proc Natl Acad Sci USA, 89 (17): 8254-8. [PMID:1518854]
7. Karecla PI, Bowden SJ, Green SJ, Kilshaw PJ. (1995) Recognition of E-cadherin on epithelial cells by the mucosal T cell integrin alpha M290 beta 7 (alpha E beta 7). Eur J Immunol, 25 (3): 852-6. [PMID:7705417]
8. Schön MP, Arya A, Murphy EA, Adams CM, Strauch UG, Agace WW, Marsal J, Donohue JP, Her H, Beier DR et al.. (1999) Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice. J Immunol, 162 (11): 6641-9. [PMID:10352281]
9. Stefanich EG, Danilenko DM, Wang H, O'Byrne S, Erickson R, Gelzleichter T, Hiraragi H, Chiu H, Ivelja S, Jeet S et al.. (2011) A humanized monoclonal antibody targeting the β7 integrin selectively blocks intestinal homing of T lymphocytes. Br J Pharmacol, 162 (8): 1855-70. [PMID:21232034]
10. Vermeire S, Ghosh S, Panes J, Dahlerup JF, Luegering A, Sirotiakova J, Strauch U, Burgess G, Spanton J, Martin SW et al.. (2011) The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study. Gut, 60 (8): 1068-75. [PMID:21317177]
11. Vermeire S, O'Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, Lamb CA, Feagan BG, Panes J, Salas A et al.. (2014) Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet, 384 (9940): 309-18. [PMID:24814090]

References

1. Cepek KL, Parker CM, Madara JL, Brenner MB. (1993)
Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells.
J Immunol, 150 (8 Pt 1): 3459-70. [PMID:8468482]

2. Feagan BG, Greenberg GR, Wild G, Fedorak RN, Paré P, McDonald JW, Dubé R, Cohen A, Steinhart AH, Landau S et al.. (2005)
Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin.
N Engl J Med, 352 (24): 2499-507. [PMID:15958805]

3. Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S et al.. (2013)
Vedolizumab as induction and maintenance therapy for ulcerative colitis.
N Engl J Med, 369 (8): 699-710. [PMID:23964932]

4. Fong S, Dennis MS. (2009)
Humanized anti-beta7 antagonists and uses therefor.
Patent number: US7528236 B2. Assignee: Genentech, Inc.. Priority date: 03/09/2004. Publication date: 09/05/2009.

5. Holzmann B, McIntyre BW, Weissman IL. (1989)
Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha.
Cell, 56 (1): 37-46. [PMID:2463092]

6. Hu MC, Crowe DT, Weissman IL, Holzmann B. (1992)
Cloning and expression of mouse integrin beta p(beta 7): a functional role in Peyer's patch-specific lymphocyte homing.
Proc Natl Acad Sci USA, 89 (17): 8254-8. [PMID:1518854]

7. Karecla PI, Bowden SJ, Green SJ, Kilshaw PJ. (1995)
Recognition of E-cadherin on epithelial cells by the mucosal T cell integrin alpha M290 beta 7 (alpha E beta 7).
Eur J Immunol, 25 (3): 852-6. [PMID:7705417]

8. Schön MP, Arya A, Murphy EA, Adams CM, Strauch UG, Agace WW, Marsal J, Donohue JP, Her H, Beier DR et al.. (1999)
Mucosal T lymphocyte numbers are selectively reduced in integrin alpha E (CD103)-deficient mice.
J Immunol, 162 (11): 6641-9. [PMID:10352281]

9. Stefanich EG, Danilenko DM, Wang H, O'Byrne S, Erickson R, Gelzleichter T, Hiraragi H, Chiu H, Ivelja S, Jeet S et al.. (2011)
A humanized monoclonal antibody targeting the β7 integrin selectively blocks intestinal homing of T lymphocytes.
Br J Pharmacol, 162 (8): 1855-70. [PMID:21232034]

10. Vermeire S, Ghosh S, Panes J, Dahlerup JF, Luegering A, Sirotiakova J, Strauch U, Burgess G, Spanton J, Martin SW et al.. (2011)
The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study.
Gut, 60 (8): 1068-75. [PMID:21317177]

11. Vermeire S, O'Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, Lamb CA, Feagan BG, Panes J, Salas A et al.. (2014)
Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial.
Lancet, 384 (9940): 309-18. [PMID:24814090]

etrolizumab

GtoPdb Ligand ID: 8407

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