Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy.

Autor: Lambright, E S, Amin, K, Wiewrodt, R, Force, S D, Lanuti, M, Propert, K J, Litzky, L, Kaiser, L R, Albelda, S M
Předmět:
Zdroj: Gene Therapy; Jun2001, Vol. 8 Issue 12, p946, 8p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
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