TREATMENT OF PLEURAL MESOTHELIOMA IN AN IMMUNOCOMPETENT RAT MODEL UTILIZING ADENOVIRAL TRANSFER OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE

Previously, we have treated malignant mesothelioma (MM) growing in the peritoneal cavity of immunodeficient mice utilizing a recombinant ade novirus vector carrying the herpes simplex virus-thymidine kinase gene (Ad.RSVtk) followed by administration of the anti-viral drug ganciclo vir (GCV). To mimic more closely the clinical situation in human MM, a syngeneic model of pleural MM was developed in immunocompetent Fische r rats. Administration of Ad.RSVtk into the pleural space of animals w ith established multifocal tumor followed by systemic GCV therapy resu lted in significant tumor regression at 20 days in HSVtk/GCV-treated a nimals (average tumor weight 0.6 +/- 0.2 gram; n = 12) versus control animals (average weight 5.4 +/- 0.2 grams; n = 21; p < 0.001). In addi tional studies, Ad.RSVtk/GCV-treated animals had a mean survival of 34 days (average tumor weight 1.0 +/- 0.3 gram at death) versus 26 days in control animals (average tumor weight 6.2 +/- 0.6 grams at death). A significant reduction in tumor burden was also seen when more advanc ed, bulkier disease was treated. These studies demonstrate the Ad.RSVt k/GCV system is effective in the treatment of pleural-based tumors in an immunocompetent host. However, there are limitations to this treatm ent approach that result in only small increments in survival.