GENE-THERAPY USING ADENOVIRUS CARRYING THE HERPES SIMPLEX-THYMIDINE KINASE GENE TO TREAT IN-VIVO MODELS OF HUMAN-MALIGNANT MESOTHELIOMA ANDLUNG-CANCER

Previous studies have shown adenoviral transfer of the herpes simplex virus thymidine kinase (HSVtk) gene followed by the anti-viral drug ga nciclovir (GCV) can be used to successfully treat established human me sothelioma tumors growing within the peritoneal cavities of severe com bined immune deficient (SCID) mice. These findings raised a number of questions important to the applicability, efficiency, and safety of th is treatment strategy. In this report, we have further characterized t he use of recombinant adenovirus carrying the HSVtk gene to treat meso thelioma and other localized malignancies. Our results indicate that t he Ad. RSVtk/GCV system is effective in causing tumor regression in an imals inoculated with another mesothelioma cell line and a lung cancer cell line and that animals with bulky disease can be successfully tre ated. Effects are seen at a wide range of virus doses and significant anti-tumor activity is present at doses of ganciclovir that are clinic ally achievable. Finally, this treatment approach appears safe, with l imited dissemination of virus using a sensitive RT-PCR detection syste m. These studies further characterize the use of adenoviral transfer o f the HSVtk gene to treat experimental mesothelioma and suggest that c linical trials using this approach may be feasible.