Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma.
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.
Harrison
L H
LH
Department of Surgery, Louisiana State University Health Sciences Center, New Orleans 70112-2822, USA. lharri@lsumc.edu
Schwarzenberger
P O
PO
Byrne
P S
PS
Marrogi
A J
AJ
Kolls
J K
JK
McCarthy
K E
KE
D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000235:genetics; D010997:Pleural Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D019275:Radiopharmaceuticals; D018139:Simplexvirus / Q000235:genetics*; D017556:Technetium Compounds; D013937:Thymidine Kinase / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D019275:Radiopharmaceuticals; D017556:Technetium Compounds; D013937:Thymidine Kinase