PLEURAL BASED MESOTHELIOMA IN IMMUNE COMPETENT RATS - A MODEL TO STUDY ADENOVIRAL GENE-TRANSFER

Background. Despite multimodality approaches, pleural-based malignant mesothelioma remains a disease with a very poor prognosis. Novel thera peutic strategies such as gene therapy clearly are needed to improve t he survival of patients with this neoplasm. To aid in the evaluation o f new treatment strategies, animal models that closely mimic human dis ease are required. This article describes the establishment of a pleur al-based model of malignant mesothelioma in immune-competent Fischer r ats. Methods. Via a modified left anterior lateral thorocotomy, a syng eneic malignant mesothelioma cell line, called II-45, was placed into the pleural cavity of Fischer rats. Results. Placement of II-45 cells into the pleural cavity of Fischer rats results in a model of pleural mesothelioma that closely resembles the disease seen in patients and i s highly reproducible, with animals dying within 1 month. We also demo nstrate the feasibility of adenoviral-mediated gene transfer to normal mesothelial cells lining the pleural cavity, as well as to malignant cells deep within the substance of pleural-based malignant mesotheliom a. Conclusions. The model described here offers the opportunity to stu dy a variety of new treatment modalities, especially somatic gene tran sfer, against pleural-based malignant mesothelioma in an immune compet ent setting.