A novel monoclonal antibody cross-reactive with both human and mouse α9 integrin useful for therapy against rheumatoid arthritis.


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
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

231-241

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Auteurs

Masaharu Torikai (M)

Research & Development Division, KM Biologics Co., Ltd, 1314-1 Kyokushi-Kawabe, Kikuchi, Kumamoto 869-1298, Japan.

Hirofumi Higuchi (H)

Research & Development Division, KM Biologics Co., Ltd, 1314-1 Kyokushi-Kawabe, Kikuchi, Kumamoto 869-1298, Japan.

Nobuchika Yamamoto (N)

Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

Daisuke Ishikawa (D)

Research & Development Division, KM Biologics Co., Ltd, 1314-1 Kyokushi-Kawabe, Kikuchi, Kumamoto 869-1298, Japan.

Hirotada Fujita (H)

Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

Katsunari Taguchi (K)

Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

Fumihiko Sakai (F)

EVEC Inc., 6 Odori Nishi, Chuo-ku, Sapporo 060-0042, Japan.

Kenji Soejima (K)

Research & Development Division, KM Biologics Co., Ltd, 1314-1 Kyokushi-Kawabe, Kikuchi, Kumamoto 869-1298, Japan.

Toshihiro Nakashima (T)

The Chemo-Sero-Therapeutic Research Institute (Kaketsuken), 4-7 Hanabatacho, Chuo-ku, Kumamoto 860-0806, Japan.

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Classifications MeSH