title: Targeting interleukin-4 receptor α with hybrid peptide for effective cancer therapy.
abstract: Interleukin-4 receptor α (IL-4Rα) chain is highly expressed on the surface of various human solid tumors. We designed a novel hybrid peptide termed IL-4Rα-lytic peptide that targets the IL-4Rα chain. The IL-4Rα-lytic peptide contains a target moiety to bind to IL-4Rα and a cellular toxic lytic peptide that selectively kills cancer cells. The anticancer activity of the IL-4Rα-lytic peptide was evaluated in vitro and in vivo. It was found that the IL-4Rα-lytic peptide has cytotoxic activity in cancer cell lines expressing IL-4Rα, determined by quantitative real-time PCR. The IC(50) ratios of the lytic peptide to the IL-4Rα-lytic peptide correlated well with the expression levels of IL-4Rα on cancer cells (r = 0.80). In addition, IL-4Rα-lytic peptide administered either intratumoraly or intravenously significantly inhibited tumor growth in xenograft model of human pancreatic cancer (BXPC-3) in mice. These results indicate that the IL-4Rα-lytic peptide generated in this study has a potent and selective anticancer potential against IL-4Rα-positive solid cancers.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto, Japan.
authors.forename: Liying
authors.initials: L
authors.lastname: Yang
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Horibe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohno
authors.forename: Mari
authors.initials: M
authors.lastname: Haramoto
authors.forename: Koji
authors.initials: K
authors.lastname: Ohara
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D057127:Single-Chain Antibodies / Q000378:metabolism* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C504000:IL4R protein, human; D000922:Immunotoxins; D053662:Interleukin-4 Receptor alpha Subunit; D010455:Peptides; D057127:Single-Chain Antibodies