Louisiana State University Medical Center and Stanley S. Scott Cancer Center

INVESTIGATORS:

Paul Schwarzenberger, M.D. (Principal Investigator)
Jay Kolls, M.D.
Scott Freeman, M.D.
Lynn Harrison, M.D.
Aizen Marrogi, M.D.
Raj. Ramesh, Ph.D.
Chris Theodossiou, M.D.

Abstract

Malignant mesothelioma is a tumor of the pleura for which there is no satisfactory treatment. It is almost universally fatal, regardless of the stage of the tumor at the time of diagnosis. Current treatment modalities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalities is superior to no treatment at all. Because of the dismal prognosis for patients with malignant mesothelioma, a new mode of treatment is desperately needed. A promising area of research into the treatment of various malignancies is gene therapy. Recent studies have demonstrated the utility of exposing tumor cells to cells transduced to express the Herpes simplex virus gene for thymidine kinase (HSV-TK). By virtue of their expression of HSV-TK, the transduced cells are rendered susceptible to the antiviral drug, ganciclovir (GCV). Nearby tumor cells are killed by a so-called bystander effect. In this protocol we propose a Phase I trial to study the safety and determine the maximal tolerated dose of an HSV-TK-transduced ovarian cancer cell line (PA1-STK cells) infused into the pleural cavities of patients with malignant pleural mesothelioma, followed by systemic administration of ganciclovir. The hope is that administration of ganciclovir will result in killing of the transduced ovarian cancer cells as well as the nearby malignant mesothelioma cells. This is a standard dose-escalation protocol.

To obtain more information regarding this protocol, please contact Dr. Paul Schwarzenberger at 504-568-5843; (504) 568-6294 or  Dr. Jay Kolls at 504-568-4634.

** POSTED DECEMBER 11, 1997 **

Antitumor Activity With Gene Modified Tumor Cells

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.

Address: 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.
Source: Am J Respir Cell Mol Biol, 19(2):333-7 1998 Aug
Author: Schwarzenberger P; Lei D; Freeman SM; Ye P; Weinacker A; Theodossiou C; Summer W; Kolls JK

*** POSTED NOVEMBER 6, 1998 ***