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  • Title: Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity.
    Author: Koike M, Nakamura K, Furuya A, Iida A, Anazawa H, Takatsu K, Hanai N.
    Journal: Hum Antibodies; 2009; 18(1-2):17-27. PubMed ID: 19478395.
    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 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.
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