Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells
- Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575 (Japan)
- Department of Microbiology and Immunity, Graduate School of Medicine, Tohoku University, Seiryo-machi 2-1, Aoba-ku, Sendai 980-8575 (Japan)
- Major of Medical Sciences, Graduate School of Comprehensive Human Sciences, Tsukuba University, Tennodai 1-1-1, Tsukuba 305-8575 (Japan)
Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human {gamma}c chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the {gamma}c chain, the cells were treated with ganciclovir (GCV). The {gamma}c chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the {gamma}c chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial.
- OSTI ID:
- 20798829
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 341, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2005.12.199; PII: S0006-291X(06)00048-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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