A novel interleukin‐13 receptor alpha 2‐targeted hybrid peptide for effective glioblastoma therapy

• Published in: Chemical biology & drug design 2019-07, Vol.94 (1), p.1402-1413
• Main Authors: Kurihara, Ryohsuke, Horibe, Tomohisa, Shimizu, Eiko, Torisawa, Aya, Gaowa, Arong, Kohno, Masayuki, Kawakami, Koji
• Format: Article
• Language: English
• Subjects: glioblastoma; hybrid peptide; IL‐13Rα2; molecularly targeted therapy; T7 phage display
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.13517

We previously designed and reported a novel class of drugs, namely hybrid peptides, which are chemically synthesized and composed of a targeted binding peptide and a lytic‐type peptide containing cationic amino acid residues that cause cancer cell death. In the present study, we screened for peptides that bind to interleukin‐13 receptor alpha 2 (IL‐13Rα2) by using a T7 random peptide phage display library system and isolated several positive phage clones. The A2b11 peptide, which was one of the positive clones, was shown to bind to IL‐13Rα2 protein by Biacore analysis and a binding assay using glioblastoma (GB) cell lines. This peptide was linked with a lytic peptide containing a linker sequence to form the IL‐13Rα2–lytic hybrid peptide. The IL‐13Rα2–lytic hybrid peptide showed cytotoxic activity against GB cell lines in vitro. The IL‐13Rα2–lytic hybrid peptide also affected Akt and Erk1/2 activation following treatment with interleukin‐13 and induced rapid ATP dynamics in GB cells. Anti‐tumor activity of the IL‐13Rα2–lytic hybrid peptide was observed in vivo after intratumoral injection in a mouse xenograft model of human GB cells. These results suggest that the IL‐13Rα2–lytic hybrid peptide might be a potent therapeutic option for patients with GB. Screening of binding peptide to IL‐13Rα2 by T7 random peptide phage display system was performed, several positive phage clones were isolated, and A2b11 peptide, which is one of the positive clones was conjugated with lytic peptide, termed as IL‐13Rα2–lytic hybrid peptide. It was found that IL‐13Rα2–lytic had cytotoxic and anti‐tumor by intratumoral administration activities against glioblastoma (GB) cell lines. It is suggested that IL‐13Rα2–lytic might provide one of the potent therapeutic options for patients with GB in the future.