Gene therapy for malignant pleural mesothelioma

Malignant mesothelioma (MM) is a fatal malignancy refractory to all forms of standard anticancer therapy. This article reports the results of a phase I clinical trial assessing the safety of intrapleural delivery and efficacy of intratumoral gene transfer of recombinant adenovirus (rAd) containing herpes simplex virus thymidine kinase (HSVtk) gene into the pleural space of patients with MM, followed by systematic treatment with the antiviral drug ganciclovir (GCV) for 14 days. AD.RSVtk/GCV gene therapy proved to be well tolerated, with evidence of significant gene transfer particularly at high vector doses and with elimination of preliminary biopsy. Ongoing gene therapy trials for mesothelioma at two other centers, focusing on immunostimulation and using suicide gene therapy as a tumor vaccine, are also reviewed in this article.