Affiliations: [a] Tokyo Research Laboratories, Kyowa Hakko Kirin, Co., Ltd, Machida-shi, Tokyo, Japan | [b] Graduate Scholl of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan
Correspondence:
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Corresponding author: Masamichi Koike, BioWa, Inc., 212 Carnegie Center Suite 101, Princeton, NJ 08540, USA. Tel.: +1 609 734 3420; E-mail: [email protected].
Abstract: 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 α and β polypeptide chains (hIL-5Rα and βc) that are expressed on the cell surface. The hIL-5Rα specifically binds IL-5 without involvement of the βc. It has been suggested that neutralizing antibodies to hIL-5Rα 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-5Rα 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.
