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  • Title: HSV-tk/GCV gene therapy mediated by EBV-LMP1 for EBV-associated cancer.
    Author: Lifang Y, Min T, Midan A, Ya C.
    Journal: J Exp Clin Cancer Res; 2008 Sep 23; 27(1):42. PubMed ID: 18811956.
    Abstract:
    BACKGROUND: To investigate the feasibility of gene therapy in treating Epstein-Barr virus (EBV)-associated cancer by employing the suicide gene, herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV), which uses the signaling pathway through the HIV-long terminal repeat (LTR) gene which is expressed from a nuclear factor-kappaB (NF-kappaB)-binding motif-containing promoter that is regulated by EBV-latent membrane protein 1 (LMP1) via NF-kappaB. METHODS: First, we constructed the plasmid pVLTR-tk, which was regulated by EBV-LMP1 via NF-kappaB, and then investigated the cytotoxic effect of the pVLTR-tk/GCV on cancer cells, using MTT assays, clonogenic assays, flow cytometry, and animal experiments. RESULTS: The activation of TK was increased after transfection of the pVLTR-tk into the EBV-LMP1 positive cells. After GCV treatment, the clonogenicity and survival of the cells substantially declined, and a bystander effect was also observed. The LMP1 positive cells exhibited remarkable apoptosis following pVLTR-tk/GCV treatment, and the pVLTR-tk/GCV restrained tumor growth in vivo for EBV-LMP1 positive cancers. CONCLUSION: The pVLTR-tk/GCV suicide gene system may be used as a new gene targeting strategy for EBV-associated cancer.
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