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

Malignant mesothelioma (MM) is a thoracic malignancy that is increasing ill 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.