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Ann Thorac Surg 2000;70:407-411
© 2000 The Society of Thoracic Surgeons

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Original articles: general thoracic

Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma

^a Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA

Address reprint requests to Dr Harrison, Department of Surgery, Louisiana State University Health Sciences Center, 1542 Tulane Ave, New Orleans, LA 70112-2822
e-mail: lharri{at}lsumc.edu

Presented at the Forty-sixth Annual Meeting of the Southern Thoracic Surgical Association, San Juan, Puerto Rico, Nov 4–6, 1999.

Background. Malignant mesothelioma is an uncommon but lethal cancer of increasing incidence, particularly among patients with a history of exposure to asbestos. Although numerous treatments have been employed, including chemotherapy, radiation therapy, surgical resection, and combinations of the above, no satisfactory treatment yet exists, and affected patients will die of this disease, usually within 12 months. Gene-based therapies constitute a new approach that offers hope of improved control of these tumors while being associated with less morbidity than conventional chemotherapeutic or surgical regimens. We demonstrated that PA1-STK cells home in vivo to mesothelioma deposits, a phenomenon that is required for optimal exertion of this therapeutic concept.

Methods. Gene-modified ovarian cancer cells expressing the thymidine-kinase gene (PA1-STK) were radiolabeled with ⁹⁹Tc and infused into the pleural space of 4 patients with malignant pleural mesothelioma, then scanned to determine distribution of the cells.

Results. PA1-STK cells recognized and adhered preferentially to mesothelioma lining the chest wall.

Conclusions. Cell-based "suicide gene" therapy utilizing the "bystander effect" with the gene-modified ovarian cancer cell line PA1-STK is feasible in human pleural mesothelioma. We have shown that this trafficking and homing of the therapeutic cells to the intrapleural tumor sites, a requirement for success with this novel therapeutic concept, is also valid in humans.

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