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Antitumor activity with the HSV-tk-gene-modified cell line PA-1-STK in malignant mesothelioma

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Antitumor activity with the HSV-tk-gene-modified cell line PA-1-STK in malignant mesothelioma AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY Schwarzenberger, P., Lei, D. H., Freeman, S. M., Ye, P., Weinacker, A., Theodossiou, C., Summer, W., Kolls, J. K. 1998; 19 (2): 333-337

Abstract

Malignant mesothelioma (MM) is a thoracic malignancy that is increasing in incidence. Since it is uniformly fatal and kills by local spread, investigators have proposed that MM is a good target for novel treatment approaches, such as gene therapy. We hypothesized that delivery of the HSV-tk gene, using gene-modified tumor cells (PA-1-STK cells), would result in an antitumor effect after treatment with ganciclovir. In in vitro mixing experiments, we found that PA-1-STK cells killed both mouse and human mesothelioma cells in a dose-dependent manner. Moreover, we found that PA-1-STK cells also prolonged survival of mice with MM when the percentage of total tumor cells was high (70%), but observed no survival benefit when the percentage of PA-1-STK cells was low (30%). These data support the rationale for a cell-based gene therapy approach to MM.

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