The development of the novel vector that eliminates ES/iPS cell-derived tumor to realize regenerative medicine

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670194
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Kagoshima University
• Principal Investigator: Kosai Ken-ichiro 鹿児島大学, 医歯学域医学系, 教授 (90258418)
• Co-Investigator(Kenkyū-buntansha): MITSUI Kaoru 鹿児島大学, 医歯学域医学系, 講師 (40324975) ; IRIE Rie 鹿児島大学, 医歯学域医学系, 助教 (90381178) ; IJICHI Nobuhiro 鹿児島大学, 医歯学域医学系, 助教 (80380624) ; WAN Yu-chin 鹿児島大学, 医歯学総合研究科, 分担研究員 (20505143)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 再生医学 / iPS細胞 / 遺伝子治療 / ウイルスベクター / 腫瘍溶解性ウイルス / サバイビン / 腫瘍化 / ES細胞

Outline of Final Research Achievements

Incomplete abolition of tumorigenicity creates potential safety concerns in clinical human pluripotent stem cells (hPSCs)-based regenerative medicine. We found that conditionally replicating adenoviruses that specifically target cancers using multiple factors (m-CRAs), originally developed as anticancer drugs, may also be useful as novel antitumorigenic agents in hPSC-based therapy. The survivin promoter was more active in undifferentiated hPSCs than the telomerase reverse transcriptase (TERT) promoter, whereas both promoters were minimally active in differentiated ones. Accordingly, survivin-responsive m-CRA (Surv.m-CRA) killed only undifferentiated hPSCs, but not undifferentiated ones, more efficiently than TERT-responsive m-CRAs (Tert.m-CRA). Pre-infection of hPSCs with Surv.m-CRA or Tert.m-CRA abolished in vivo teratoma formation following hPSC implantation into mice. Thus, m-CRAs may be novel antitumorigenic agents in hPSC-based regenerative medicine.

Free Research Field

医歯薬学