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 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.
Schwarzenberger
P
P
Sections of Hematology/Oncology and Pulmonary/Critical Care, and the Stanley S. Scott Cancer Center Gene Therapy Program, Louisiana State University Medical Center, New Orleans, LA, USA.
Lei
D
D
Freeman
S M
SM
Ye
P
P
Weinacker
A
A
Theodossiou
C
C
Summer
W
W
Kolls
J K
JK
D000818:Animals; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D013937:Thymidine Kinase; D015774:Ganciclovir