A novel monoclonal antibody cross-reactive with both human and mouse α9 integrin useful for therapy against rheumatoid arthritis.
Animals
Antibodies, Monoclonal
/ immunology
Arthritis, Rheumatoid
/ drug therapy
Cell Adhesion
/ drug effects
Cell Differentiation
/ drug effects
Cell Line, Tumor
Cell Surface Display Techniques
Cross Reactions
Disease Models, Animal
Green Fluorescent Proteins
/ genetics
Humans
Immunoglobulin Variable Region
/ immunology
Inflammation
/ drug therapy
Integrin alpha Chains
/ genetics
Male
Mice
Mice, Inbred DBA
Osteoclasts
/ metabolism
Transfection
Treatment Outcome
anti-α9 integrin antibody
cross-reactivity
phage display technology
rheumatoid arthritis
therapeutic antibody
Journal
Journal of biochemistry
ISSN: 1756-2651
Titre abrégé: J Biochem
Pays: England
ID NLM: 0376600
Informations de publication
Date de publication:
01 Sep 2020
01 Sep 2020
Historique:
received:
14
11
2019
accepted:
28
03
2020
pubmed:
10
4
2020
medline:
9
2
2021
entrez:
10
4
2020
Statut:
ppublish
Résumé
This study introduces a novel monoclonal anti-α9 integrin antibody (MA9-413) with human variable regions, isolated by phage display technology. MA9-413 specifically binds to both human and mouse α9 integrin by recognizing a conserved loop region designated as L1 (amino acids 104-122 of human α9 integrin). MA9-413 inhibits human and mouse α9 integrin-dependent cell adhesion to ligands and suppresses synovial inflammation and osteoclast activation in a mouse model of arthritis. This is the first monoclonal anti-α9 integrin antibody that can react with and functionally inhibit both human and mouse α9 integrin. MA9-413 allows data acquisition both in animal and human pharmacological studies without resorting to surrogate antibodies. Since MA9-413 showed certain therapeutic effects in the mouse arthritis model, it can be considered as a useful therapy against rheumatoid arthritis and other α9 integrin-associated diseases.
Identifiants
pubmed: 32271918
pii: 5818496
doi: 10.1093/jb/mvaa040
doi:
Substances chimiques
Antibodies, Monoclonal
0
Immunoglobulin Variable Region
0
Integrin alpha Chains
0
enhanced green fluorescent protein
0
integrin alpha9
0
Green Fluorescent Proteins
147336-22-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
231-241Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.