期刊
GENE THERAPY
卷 8, 期 12, 页码 946-953出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3301489
关键词
herpes simplex thymidine kinase; adenovirus; replicating adenovirus; gene therapy; cancer gene therapy
类别
资金
- NCI NIH HHS [P50-CA-83638] Funding Source: Medline
- PHS HHS [P01 66726] Funding Source: Medline
Replication-incompetent adenoviruses (Ad) carrying the herpes simplex thymidine kinase (HSVtk) gene have been used in a number of human cancer gene therapy trials, however transduction has generally been limited to a small minority of tumor cells. To solve this problem, replication-competent adenoviral Vectors carrying transgenes such as HSVtk have been developed. However, contradictory evidence exists regarding the efficacy of these new vectors. Accordingly, we constructed and tested a replication-competent E3-deleted adenoviral vector containing the HSVtk suicide gene driven by the endogenous E3 promoter (Ad.wt.tk). This virus showed high level production of the HSVtk transgene and was more efficacious than a non-replicating virus in vitro, after injection into flank tumors, and against established intraperitoneal tumors. However, addition of ganciclovir (GCV) therapy to cells or tumor-bearing animals treated with the replicating vector containing the HSVtk suicide gene did not result in increased cell killing. Our results indicate that addition of HSVtk to a replicating Ad Virus will not likely be useful in augmenting antitumor effects.
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