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.