Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
France

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Suicide Gene Therapy Mediated by the Herpes Simplex Virus Thymidine Kinase Gene / Ganciclovir System: Fifteen Years of Application

Author(s): C. Fillat, M. Carrio, A. Cascante and B. Sangro

Affiliation: Cristina Fillat, Centre de Regulacio Genomica (CRG). Passeig Maritim 37-49. 08003- Barcelona, Spain

Keywords: hsvtr/gc, gene-directed enzyme prodrug therapy, gdept, suicide gene therap, herpes simplex virus, thymidine kinese gene, ganciclovir system hsvtr

Abstract:

Gene-directed enzyme prodrug therapy (GDEPT) is a two step therapeutic approach for cancer gene therapy. In the first step, the transgene is delivered into the tumor and expressed. In the second step a prodrug is administered and is selectively activated by the expressed enzyme. The first GDEPT system described was the thymidine kinase gene of the Herpes Simplex virus (HSVtk) in combination with the prodrug Ganciclovir (GCV). A large number of experiments have been performed with this system, in different types of tumors and initial studies in animal models were very promising. This encouraged investigators to move into clinical trials although poor results have been obtained so far. A large effort has been made with numerous different strategies to enhance HSVtk / GCV efficacy in cellular and in vivo models and very strong cytotoxic effects have been obtained. The present review describes the current state of preclinical research and summarizes the results of the clinical trials undertaken.

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Article Details

VOLUME: 3
ISSUE: 1
Page: [13 - 26]
Pages: 14
DOI: 10.2174/1566523033347426