Gene therapy of adult T cell leukemia stem cell

• 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
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• 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 / HTLV-1 bZIP factor / 成人T細胞白血病幹細胞 / 癌特異的増殖型デノウイルス / ウイルス由来遺伝子 / 癌特異的増殖型アデノウイ ルス / 白血病幹細胞 / 成人Ｔ細胞白血病

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.

Research Products

• [Journal Article] Effects of exogenous interleukin-7 on CD8(+) T-cell survival and function in human T-cell lymphotropic virus type 1 infection. (2013)
  • Author(s): White Y, Yoshimitsu M, Kozako T, Matsushita K, Koriyama C, Uozumi K, Suzuki S, Kofune H, Arima N.
  • Journal Title: Leukemia and Lymphoma. Volume: 54 Issue: 10 Pages: 2243-2250
  • DOI: 10.3109/10428194.2013.772174
  • Peer Reviewed
• [Presentation] Graft versus ATLL effect for relapse after allogeneic stem cell transplantation (2013)
  • Author(s): Daisuke Nakamura, Shinsuke Suzuki, et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌（札幌市）
• [Presentation] Clinical experience of POEMs syndrome in our institution (2013)
  • Author(s): Maiko Hayashida, Shinsuke Suzuki, et al.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌（札幌市）
• [Presentation] Cell death in ATL cell lines by survivin-responsive conditionally replicatin g adenoviruses. (2011)
  • Author(s): 鈴木紳介 魚住公治 小戝健一郎 有馬直道
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場