27. TREATMENT OF PATIENTS WITH MALIGNANT MESOTHELIOMA WITH THE GENE MODIFIED CELL LINE PA1-STK: PRELIMINARY RESULTS OF A PHASE 1 TRIAL.
Lynn Harrison, Patrick Byrne, Jay K. Kolls, Scott Freeman, Aizen Marrogi, Tajagopal Ramesh, Chris Theodossiou, Richard Gaumer, Warren Summer, Ann Weinacker and Paul O. Schwarzenberger*
Louisiana State University Medical Center
New Orleans, Louisiana, USA
BACKGROUND
Our group has developed a clinical phase I study for the treatment of malignant mesothelioma using PA1-STK cells [an ovarian cancer cell line that was genetically modified to encode the Herpes simplex thymidine kinase gene (HSV-tk)].
METHODS AND RESULTS
These cells are injected intrapleurally in a dose-escalated fashion. Cell administration is followed by one-week administration of ganciclovir (GCV). Preliminary data using Technetium labeling of PA1-STK cells demonstrates that these gene-modified cells can attach to tumor cells in mesothelioma patients. We hypothesize that these cells can kill nearby tumor cells upon administration of GCV via the "bystander effect." To date, we have treated 12 patients with a maximal dose of 3 x 109 cells. The treatment has been well tolerated without any apparent toxicity defined by the NCI criteria. A significant change in the composition of lymphocytes obtained from malignant pleural effusions was demonstrated during the treatment: CD4 cells expressing CD28 increased by 67% and CD8 cells coexpressing CD62L and CD45RA by 57%.
CONCLUSION
These results indicate that intrapleural infusion of the HSV-tk suicide gene therapy at a dose of 3 x 109 cells is safe. Moreover, the treatment has effects on intrapleural T-cells that need to be further defined.
