Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity.
Human interleukin-5 is the key cytokine involved in regulating the production and function of human eosinophils. IL-5 binds to its specific receptor composed of two heterogeneous alpha and beta polypeptide chains (hIL-5Ralpha and betac) that are expressed on the cell surface. The hIL-5Ralpha specifically binds IL-5 without involvement of the betac. It has been suggested that neutralizing antibodies to hIL-5Ralpha could serve as a therapeutic agent in eosinophil-associated diseases. We describe here the creation and biologic activities of a mouse monoclonal antibody against hIL-5Ralpha that blocks the following IL-5 dependent activities (a) binding of the IL-5 ligand to its receptor, (b) IL-5 dependent growth of hIL-5R expressing cells, and (c) IL-5-induced adhesion of human eosinophils. We also describe the process for humanization of the mouse Mab towards development of a therapeutic MAb. The humanized version of the monoclonal antibody also displayed potent neutralizing activity against IL-5 dependent activities.
Koike
Masamichi
M
Tokyo Research Laboratories, Kyowa Hakko Kirin, Co., Ltd, Machida-shi, Tokyo, Japan. masamichi.koike@biowa.com
Nakamura
Kazuyasu
K
Furuya
Akiko
A
Iida
Akihoro
A
Anazawa
Hideharu
H
Takatsu
Kiyoshi
K
Hanai
Nobuo
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D007114:Immunization; D053666:Interleukin-5 Receptor alpha Subunit / Q000037:antagonists & inhibitors* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D015202:Protein Engineering; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; C485918:IL5RA protein, human; D053666:Interleukin-5 Receptor alpha Subunit; D011994:Recombinant Proteins