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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 (IC 50 ) 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.

Targeting Interleukin-4 Receptor Alpha by Hybrid Peptide for Novel Biliary Tract Cancer Therapy