Project/Area Number |
22590755
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | University of Tsukuba |
Principal Investigator |
ABEI Masato 筑波大学, 医学医療系, 准教授 (20261802)
|
Co-Investigator(Kenkyū-buntansha) |
HYODO Ichinosuke 筑波大学, 医学医療系, 教授 (60416469)
FUKUDA Kuniaki 筑波大学, 医学医療系, 講師 (50447257)
HAMADA Hirofumi 東京薬科大学, 生命科学部, 教授 (00189614)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 腫瘍融解ウイルス / 遺伝子治療 / アデノウイルス / サイクロフォスファマイド / 5-fluorouracil / UPRT / 遺伝子化学療法 / 胆道癌 |
Research Abstract |
Oncolytic viruses offer great promise as cancer therapeutics, but host antiviral immunity must be overcome for their efficacy. In this study, we demonstrated the efficacy and safety of an oncolytic adenovirus (OAd) expressing uracil phosphoribosyltransferase (UPRT), which greatly enhances the sensitivity of cancer cells to 5-fluorouracil, and further enhancement of this efficacy by a high-dose or clinically-approved safe dose of the immunosuppressive agent cyclophosphamide (CP) in Syrian hamsters with or without preexisting immunity. This is the first study demonstrating enhancement by CP of the efficacy of an OAd armed with a therapeutic gene in Ad-permissive immunocompetent animals, indicating the ability of CP to overcome the hurdle of antiviral immunity for effective virus-gene therapy.
|