Journal of Neuro-Oncology

, Volume 116, Issue 1, pp 49–57 | Cite as

Double suicide gene therapy using human neural stem cells against glioblastoma: double safety measures

  • Ji Yeoun Lee
  • Do-Hun Lee
  • Hyung A. Kim
  • Seung-Ah Choi
  • Hong Jun Lee
  • Chul-Kee Park
  • Ji Hoon Phi
  • Kyu-Chang Wang
  • Seung U. KimEmail author
  • Seung-Ki KimEmail author
Laboratory Investigation


With recent advancements in stem cell-based gene therapy, concerns about safety have grown. Stem cell-based gene therapies may pose the risk of immunological problems and oncogenesis. We investigated the feasibility of treating glioblastomas with neural stem cells [(NSCs), HB1.F3 cells] expressing double prodrug enzymes [cytosine deaminase (CD) and tyrosine kinase (TK)] to eliminate the NSCs following treatment for safety purposes. First, the in vitro and in vivo therapeutic efficacies of NSCs engineered with double prodrug enzymes (HB1.F3-CD.TK cells) were compared to cells expressing a single prodrug enzyme (HB1.F3-CD). Second, the degree of safety achieved by NSC elimination was compared with an in vitro viability assay of the NSCs after treatment with the double prodrugs. We further compared the differences in in vivo proliferation of control, single prodrug enzyme and double prodrug enzyme expressing NSCs. HB1.F3-CD.TK cells showed a better or comparable treatment outcome than HB1.F3-CD cells in vitro and in vivo. For safety, HB1.F3-CD.TK cells showed the least viability in vitro after treatment with prodrugs compared to HB1.F3 and HB1.F3-CD cells. Additionally, the in vivo proliferation among the injected NSCs found in the tumor was the smallest for HB1.F3-CD.TK cells. Double-prodrug enzyme-directed gene therapy shows good therapeutic efficacy as well as efficient eradication of the NSCs to ensure safety for clinical applications of stem cell-based gene therapies.


Neural stem cell Stem cell-based gene therapy Double suicide gene Safety 



This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012011770).

Conflict of interest

The authors have no conflict of interest to disclose.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ji Yeoun Lee
    • 1
    • 2
  • Do-Hun Lee
    • 3
  • Hyung A. Kim
    • 1
    • 2
  • Seung-Ah Choi
    • 1
    • 2
  • Hong Jun Lee
    • 4
  • Chul-Kee Park
    • 5
  • Ji Hoon Phi
    • 1
    • 2
  • Kyu-Chang Wang
    • 1
  • Seung U. Kim
    • 4
    • 6
    Email author
  • Seung-Ki Kim
    • 1
    • 2
    Email author
  1. 1.Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children’s HospitalSeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Adolescent Cancer CenterSeoul National University Cancer HospitalSeoulRepublic of Korea
  3. 3.Miami Project to Cure Paralysis, Department of Neurological Surgery, Miller School of MedicineUniversity of MiamiMiamiUSA
  4. 4.Medical Research InstituteChung-Ang University College of MedicineSeoulRepublic of Korea
  5. 5.Department of Neurosurgery, Seoul National University HospitalSeoul National University College of MedicineSeoulRepublic of Korea
  6. 6.Division of Neurology, Department of Medicine, UBC HospitalUniversity of British ColumbiaVancouverCanada

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