Study of the suicide gene therapy using HSVtk gene and GCV for oral cancer

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Gene therapy offers the possibility of new approach to cancer treatment. The purpose of this study was to test the feasibility of suicide gene therapy using herpes simplex virus thymidine kinase (HSVtk) gene and ganciclovir (GCV) for oral cancer. Four human oral squamous cell carcinoma sell lines were used. To evaluate transduction efficiency, each cell line was transduced in vitro with an adenovirus vector (Ad) or adeno-associated virus vector (AAV) containing the β-galactosidase gene. By 24 hours after transduction, nearly 100% of the cells were transduced at a multiplicity of infection (MOI) of 10, and from 10 to 30% at a MOI of 1 in Ad. Transduction efficiency in AAV was nearly 100% at a MOI of 10000, and from 40 to 50% at a MOI of 1000. Next, each cell line was transduced with an Ad or AAV containing the HSVtk gene, and subsequent administration of GCV for the assessment of suicide gene therapy. Subsequent administration of GCV resulted in complete tumor cell death. Ad or AAV containing the HSVtk gene injection followed by intraperiotoneal GCV administration inhibited remarkably tumor growth in the nude mice to which oral squamous cell carcinoma cell SAS was transplanted SCID mouse. These results suggest that suicide gene therapy with HSVtk and GCV has revealed an effective treatment strategy for the oral cancer.