scholarly journals Different efficacy of in vivo herpes simplex virus thymidine kinase gene transduction and ganciclovir treatment on the inhibition of tumor growth of murine and human melanoma cells and rat glioblastoma cells

1999 ◽  
Vol 6 (4) ◽  
pp. 358-366 ◽  
Author(s):  
Mariana Berenstein ◽  
Soraya Adris ◽  
Fernanda Ledda ◽  
Claudia Wolfmann ◽  
Jorge Medina ◽  
...  
1996 ◽  
Vol 106 (6) ◽  
pp. 1163-1168 ◽  
Author(s):  
Bernd Bonnekoh ◽  
David A. Greenhalgh ◽  
Donnie S. Bundman ◽  
Ken-ichiro Kosai ◽  
Shu-Hsia Chen ◽  
...  

2000 ◽  
Vol 27 (3) ◽  
pp. 283-291 ◽  
Author(s):  
Roland Haubner ◽  
Norbert Avril ◽  
Petros A. Hantzopoulos ◽  
Bernd Gansbacher ◽  
Markus Schwaiger

Blood ◽  
2001 ◽  
Vol 97 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Marina I. Garin ◽  
Elaine Garrett ◽  
Pierre Tiberghien ◽  
Jane F. Apperley ◽  
David Chalmers ◽  
...  

Abstract The herpes simplex virus thymidine kinase gene type 1 (HSV-Tk) ganciclovir (GCV) system is a novel therapeutic strategy for the modulation of graft-versus-host disease (GVHD), a major complication of allogeneic stem cell transplantation (allo-SCT). Retroviral-mediated gene transfer of the HSV-Tk gene into donor T lymphocytes before allo-SCT may allow their in vivo selective depletion after treatment with GCV. The expression of theHSV-Tk gene was analyzed in vitro in CEM cells, a human lymphoblastoid cell line, transduced with 2 different vectors, each containing the HSV-Tk gene and a selectable marker gene. GCV-resistant clones were identified within the clones expressing the marker gene. Characterization of the molecular events leading to this resistance revealed a 227-bp deletion in the HSV-Tk gene due to the presence of cryptic splice donor and acceptor sites within the HSV-Tk gene sequence. Furthermore, it was confirmed that this deletion was present in human primary T cells transduced with either vector and in 12 patients who received transduced donor T cells, together with a T-cell–depleted allo-SCT. In vivo circulating transduced T cells containing the truncated HSV-Tk gene were identified in all patients immediately after infusion and up to 800 days after transplantation. In patients who received GCV as treatment for GVHD, a progressive increase in the proportion of transduced donor T cells carrying the deleted HSV-Tkgene was observed. These results suggest that the limitations within the HSV-Tk/GCV system can be improved by developing optimized retroviral vectors to ensure maximal killing ofHSV-Tk–transduced cells.


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