Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity
Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity
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DOI：
10.3233/hab-2009-0198
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发表时间：
2009-01-01
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影响因子：
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通讯作者：
Hanai, Nobuo
中科院分区：
文献类型：
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作者：
Koike, Masamichi;Nakamura, Kazuyasu;Hanai, Nobuo
人白细胞介素-5是参与调节人嗜酸性粒细胞的产生和功能的关键细胞因子。IL-5与其特异性受体结合，所述受体由在细胞表面上表达的两条异质α和β多肽链（hIL-5 R α和β c）组成。hIL-5 R α特异性结合IL-5而不涉及β c。已经提出，针对hIL-5 R α的中和抗体可以用作嗜酸性粒细胞相关疾病的治疗剂。我们在此描述了抗hIL-5 R α的小鼠单克隆抗体的产生和生物学活性，该抗体阻断以下IL-5依赖性活性：（a）IL-5配体与其受体的结合，（B）表达hIL-5 R的细胞的IL-5依赖性生长，和（c）IL-5诱导的人嗜酸性粒细胞的粘附。我们还描述了小鼠单克隆抗体人源化的过程，以开发治疗性单克隆抗体。单克隆抗体的人源化版本也显示出针对IL-5依赖性活性的有效中和活性。
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-5R alpha and beta c) that are expressed on the cell surface. The hIL-5R alpha specifically binds IL-5 without involvement of the beta c. It has been suggested that neutralizing antibodies to hIL-5R alpha 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-5R alpha 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.