Development of new bio-therapy with chimeric peptide target tumor cell surface molecules of oral cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390449
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: University of Tsukuba
• Principal Investigator: BUKAWA HIROKI 筑波大学, 医学医療系, 教授 (80173558)
• Co-Investigator(Kenkyū-buntansha): SHODA Junichi 筑波大学, 医学医療系, 教授 (90241827) ; KAWAKAMI Koji 京都大学, 大学院医学研究科, 教授 (70422318)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: キメラペプチド / IL-4R / 口腔がん

Outline of Final Research Achievements

Interleukin-4 receptor α (IL-4Rα) is highly expressed on the surface of oral squamous cell carcinoma (OSCC). We designed a novel IL-4Rα-lytic hybrid peptide composed of a binding peptide to IL-4Rα and a cell-lytic peptide. We evaluated the antitumor activity of the IL-4Rα-lytic hybrid peptide as a novel molecular-targeted therapy in OSCC. Immunoblot analysis revealed that IL-4Rα was expressed in all tested OSCC cell lines, but not in a human normal keratinocyte (HaCaT) cell line. Immunohistochemical expression levels of IL-4Rα in OSCC tissues were higher compared to those in normal epithelial tissue. The IL-4Rα-lytic hybrid peptide showed cytotoxic activity in cancer cell lines with a concentration that killed 50% of all cells (IC50) as low as 10uM. HaCaT cells were less sensitive to this peptide with an IC50 of >30uM. In addition, intratumoral administration of IL-4Rα-lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human OSCC in vivo.

Free Research Field

口腔がん分野における分子生物学的研究