Gene therapy for head and neck cancer using replication-selective adenoviral vector

• Project/Area Number: 25670717
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Kobe University
• Principal Investigator: KEN-ICHI Nibu 神戸大学, 医学(系)研究科(研究院), 教授 (20251283)
• Co-Investigator(Kenkyū-buntansha): OTSUKI Naoki 神戸大学, 大学院医学研究科, 准教授 (40343264)
• Co-Investigator(Renkei-kenkyūsha): SHIRAKAWA Toshirou 神戸大学, 大学院保健学研究科, 准教授 (70335446)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: gene therapy / head and neck cancer / adenoviral vector / replication-selective / siRNA / VEGF / Midkine / アデノウイルスベクター / EGFR / 増殖制限型 / 増殖制限型アデノウイルス / 扁平上皮癌 / midkine

Outline of Final Research Achievements

A conditional replication-selective adenovirus vector in which the expression of E1a and E1b, required for viral replication, are controlled by the Midkine promoter, Ad-MK-E1, was generated.
To further enhance the oncolytic activity of Ad-MK-E1a, we integrated gene-expressing siRNA against VEGF to Ad-MK-E1 and generated Ad-MK-siVEGF. In vitro assays showed significant growth suppression not only in the cell lines expressing strong Midkine but also in the cell lines expressing weak Midkine, in comparison with adenoviral vector containing LacZ.

Research Products

• [Journal Article] A combined lymphokine-activated killer (LAK) cell immunotherapy and adenovirus-p53 gene therapy for head and neck squamous cell carcinoma (2014)
  • Author(s): Saito H, Ando S, Morishita N, Lee KM, Dator D, Dy D, Shigemura K, Adhim Z, Nibu K, Fujisawa M, Shirakawa T
  • Journal Title: Anticancer Res Volume: 34 Pages: 3365-3370
  • Peer Reviewed