Adenoviral Gene Therapy for Malignant Pleural Mesothelioma
Daniel H. Sterman, Larry R. Kaiser, and Steven M. Albelda
Malignant mesothelioma is a primary neoplasm of the mesothelial lining of the pleural (80%) or peritoneal cavities (19.5%). It has been linked conclusively to prior exposure to asbestos and may also be associated with certain genetic predispositions and past viral exposures, including SV40. Although relatively rare, mesothelioma accounts for approximately 3000 deaths per year in the United States. To date, standard treatment for mesothelioma (including surgical resection, radiation therapy, and chemotherapy) have not proven effective in significantly prolonging patient survival. A number of characteristics make this tumor an attractive target for gene therapy. First is the absence of any currently effective therapy. Second is its unique accessibility in the pleural space for vector delivery, biopsy, and subsequent analysis of treatment effects. A surgical “debulking” procedure to remove gross disease, followed by gene therapy to remove residual disease, would thus be technically feasible. Third, local extension of disease, rather than distant metastases, is responsible for the morbidity and mortality associated with this neoplasm. Thus, unlike other more widespread neoplasms, small increments of improvement in local control could engender significant improvements in palliation or survival.