Gene therapy of adult T cell leukemia stem cell

2014 Fiscal Year Final Research Report

• Project/Area Number: 23591398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kagoshima University
• Principal Investigator: SUZUKI Shinsuke 鹿児島大学, 医歯(薬)学総合研究科, 助教 (20437974)
• Co-Investigator(Renkei-kenkyūsha): KOSAI Kenichirou 鹿児島大学大学院医歯学総合研究科先進治療科学専攻運動機能修復学講座遺伝子治療, 再生医学分野, 教授 (90258418)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 癌特異的増殖型アデノウイルス / 成人T細胞白血病 / サービビン

Outline of Final Research Achievements

Adult T-cell leukemia (ATL) develops after long-term infection with the human T-cell leukemia virus type I (HTLV-1). Survivin-responsive conditionally replicating adenoviruses (Surv.CRAs) in which expression of the adenoviral early region 1A (E1A) gene is regulated by the survivin promoter, has been demonstrated to treat a variety of cancers. Six ATL cell lines were infected with Surv.CRAs at a various multiplicity of infection. The survivin promoter was strongly activated in 6 cell lines. Moreover, the expression of the coxsackie and adenovirus receptor (CAR), important for cell infection by adenoviruses, was highly upregulated in these cell lines. In contrast, weak activation of the survivin promoter and low expression of CAR were observed in peripheral blood lymphocytes (PBLs) of healthy subjects. Surv.CRAs efficiently replicated and induced cell death in 5 out of 6 cell lines compared to minimal viral replication in normal PBLs, in which there was no significant cytotoxicity.

Free Research Field

造血器腫瘍