Bimekizumab, a Novel Humanized IgG1 Antibody That Neutralizes Both IL-17A and IL-17F.
Animals
Anti-Inflammatory Agents
/ immunology
Antibodies, Monoclonal, Humanized
/ immunology
Antibodies, Neutralizing
/ immunology
Antibody Affinity
Antibody Specificity
CHO Cells
Computer Simulation
Cricetulus
Humans
Interleukin-17
/ antagonists & inhibitors
Macaca fascicularis
Models, Biological
Psoriasis
/ drug therapy
Spondylitis, Ankylosing
/ drug therapy
IL-17A
IL-17F
anti-IL-17A
bimekizumab
dual neutralization
dual targeting
monoclonal antibody
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
13
12
2019
accepted:
14
07
2020
entrez:
25
9
2020
pubmed:
26
9
2020
medline:
20
4
2021
Statut:
epublish
Résumé
Interleukin (IL)-17A is a key driver of inflammation and the principal target of anti-IL-17 therapeutic monoclonal antibodies. IL-17A, and its structurally similar family member IL-17F, have been shown to be functionally dysregulated in certain human immune-mediated inflammatory diseases such as psoriasis, psoriatic arthritis, and axial spondyloarthritis. Given the overlapping biology of these two cytokines, we postulated that dual neutralization of IL-17A and IL-17F may provide a greater depth of clinical response in IL-17-mediated diseases than IL-17A inhibition alone. We identified 496.g1, a humanized antibody with strong affinity for IL-17A but poor affinity for IL-17F. Affinity maturation of 496.g1 to 496.g3 greatly enhanced the affinity of the Fab fragment for IL-17F while retaining strong binding to IL-17A. As an IgG1, the affinity for IL-17A and IL-17F was 3.2 pM and 23 pM, respectively. Comparison of 496.g3 IgG1 with the commercially available anti-IL-17A monoclonal antibodies ixekizumab and secukinumab, by surface plasmon resonance and in a human
Identifiants
pubmed: 32973785
doi: 10.3389/fimmu.2020.01894
pmc: PMC7473305
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antibodies, Monoclonal, Humanized
0
Antibodies, Neutralizing
0
IL17A protein, human
0
IL17F protein, human
0
Interleukin-17
0
bimekizumab
09495UIM6V
ixekizumab
BTY153760O
secukinumab
DLG4EML025
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1894Informations de copyright
Copyright © 2020 Adams, Maroof, Baker, Lawson, Oliver, Paveley, Rapecki, Shaw, Vajjah, West and Griffiths.
Références
J Allergy Clin Immunol. 2017 Mar;139(3):923-932.e8
pubmed: 27502297
J Immunol. 2008 Aug 15;181(4):2799-805
pubmed: 18684971
Lancet. 2015 Aug 8;386(9993):541-51
pubmed: 26072109
Cell Res. 2007 May;17(5):435-40
pubmed: 17452998
EMBO J. 2001 Oct 1;20(19):5332-41
pubmed: 11574464
Immunity. 2009 Jan 16;30(1):108-19
pubmed: 19144317
Ann Rheum Dis. 2020 May;79(5):595-604
pubmed: 32253184
Immunity. 2002 Sep;17(3):375-87
pubmed: 12354389
Sci Rep. 2017 Jun 2;7(1):2707
pubmed: 28578388
Arthritis Res Ther. 2014 Aug 22;16(4):426
pubmed: 25146432
J Immunol. 1993 Jun 15;150(12):5445-56
pubmed: 8390535
Cytokine. 2009 Apr;46(1):7-11
pubmed: 19233684
Eur J Immunol. 2020 Apr;50(4):568-580
pubmed: 31850514
J Ethnopharmacol. 2013 Aug 26;149(1):169-75
pubmed: 23806866
Biotechnol Prog. 2013 May-Jun;29(3):697-706
pubmed: 23335490
J Pharm Sci. 2004 Nov;93(11):2645-68
pubmed: 15389672
Br J Clin Pharmacol. 2017 May;83(5):991-1001
pubmed: 27859546
Chest. 2010 Nov;138(5):1140-7
pubmed: 20538817
Nat Rev Immunol. 2009 Aug;9(8):556-67
pubmed: 19575028
MAbs. 2010 Sep-Oct;2(5):576-88
pubmed: 20676036
Ann Rheum Dis. 2011 Feb;70(2):341-8
pubmed: 21109515
Nat Med. 2013 Jul;19(7):822-4
pubmed: 23836224
Biochem Biophys Res Commun. 2007 Apr 13;355(3):751-7
pubmed: 17321501
J Immunol. 2006 Jul 1;177(1):566-73
pubmed: 16785554
J Immunol. 2009 Mar 1;182(5):3112-20
pubmed: 19234208
J Exp Med. 2008 May 12;205(5):1063-75
pubmed: 18411338
Immunity. 2011 Feb 25;34(2):149-62
pubmed: 21349428
J Inflamm Res. 2016 Apr 19;9:39-50
pubmed: 27143947
Int J Mol Sci. 2015 Dec 29;17(1):
pubmed: 26729099
J Am Acad Dermatol. 2015 Sep;73(3):400-9
pubmed: 26092291
J Immunol. 2003 Dec 1;171(11):6173-7
pubmed: 14634133
Br J Dermatol. 2009 Feb;160(2):319-24
pubmed: 19016708
J Am Acad Dermatol. 2018 Aug;79(2):277-286.e10
pubmed: 29609013
Science. 2011 Apr 1;332(6025):65-8
pubmed: 21350122
Ann Rheum Dis. 2018 Apr;77(4):523-532
pubmed: 29275332
J Biol Chem. 2007 May 4;282(18):13447-55
pubmed: 17355969
Arthritis Rheumatol. 2019 Apr;71(4):612-625
pubmed: 30390386