title: Targeting interleukin-4 receptor alpha by hybrid Peptide for novel biliary tract cancer therapy.
abstract: It is known that the interleukin-4 receptor α (IL-4R α ) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4R α -lytic hybrid peptide composed of binding peptide to IL-4R α and cell-lytic peptide and reported that the designed IL-4R α -lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4R α . Here, we evaluated the antitumor activity of the IL-4R α -lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4R α -lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5  μ M. We also showed that IL-4R α -lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4R α -lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4R α -lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan ; Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kahori
authors.identifier: 0000-0002-7266-6093
authors.initials: K
authors.lastname: Seto
authors.affiliation: Medical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shoda
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Horibe
authors.affiliation: Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Warabi
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Department of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Clinical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bukawa
authors.affiliation: Department of Human Pathology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami