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

Research Project

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
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000) Fiscal Year 2014: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2012: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords	キメラペプチド / IL-4R / 口腔がん / 臨床腫瘍学
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.