Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity

Hum Antibodies. 2009;18(1-2):17-27. doi: 10.3233/HAB-2009-0198.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / pharmacology
  • Cell Line
  • Eosinophils / immunology
  • Humans
  • Immunization
  • Interleukin-5 Receptor alpha Subunit / antagonists & inhibitors*
  • Interleukin-5 Receptor alpha Subunit / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Protein Engineering
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • IL5RA protein, human
  • Interleukin-5 Receptor alpha Subunit
  • Recombinant Proteins