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A Novel Peptide Specifically Binding to Interleukin-6 Receptor (gp80) Inhibits Angiogenesis and Tumor Growth

¹ Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology, National Taiwan University College of Medicine and Departments of ² Oncology, ³ Obstetrics and Gynecology, ⁴ Surgery, and ⁵ Traumatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Requests for reprints: Lin-Hung Wei, Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. Phone: 886-2-2312-3456, ext. 7140; Fax: 886-2-2371-1174; E-mail: weilh{at}ha.mc.ntu.edu.tw.

Experimental and clinical findings support the essential role of interleukin (IL)-6 in the pathogenesis of various human cancers and provide a rationale for targeted therapeutic investigations. A novel peptide, S7, which selectively binds to IL-6 receptor (IL-6R) chain (gp80) and broadly inhibits IL-6-mediated events, was identified using phage display library screening. The synthetic S7 peptide specifically bound to soluble IL-6R as well as cognate human IL-6R, resulting in a dose-dependent blockade of the interaction between IL-6 and IL-6R. S7 peptide prevents IL-6–mediated survival signaling and sensitizes cervical cancer cells to chemotherapeutic compounds in vitro. The in vitro analysis of antiangiogenic activity showed that S7 peptide substantially inhibits IL-6–induced vascular endothelial growth factor-A expression and angiogenesis in different cancer cell lines. Furthermore, S7 peptide was bioavailable in vivo, leading to a significant suppression of IL-6–induced vascular endothelial growth factor–mediated cervical tumor growth in severe combined immunodeficient mice. These observations show the feasibility of targeting IL-6/IL-6R interaction using the small peptide and highlight its potential in the clinical applications.

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