Mesothelioma Cells - Treatment for Malignant Mesothelioma
Promising Gene Therapy in Treatment of Malignant Mesothelioma
Modified, nonneurovirulent herpes simplex viruses (HSVs) have shown promise in treatment of brain tumors. However, HSV-1 can infect and cause disintegration of a wide variety of cell types. HSV-1716, a mutant of the virus lacking both copies of the gene coding ICP-34.5, can effectively treat a localized intraperitoneal malignancy. Human malignant mesothelioma cells supported the growth of HSV-1716 and efficiently disintegrated in vitro. Intraperitoneal injection of HSV-1716 into animals with established tumor nodules reduced tumor burden and significantly prolonged survival in an animal model of non-central nervous system-localized human malignancy, without dissemination or persistence, after intraperitoneal injection into mice bearing human tumors. These findings suggest that this virus may be efficacious and safe for use in localized human malignancies of non-neural origin such as malignant mesothelioma. "Use of a 'replication-restricted' herpes virus to treat experimental human malignant mesothelioma", Kucharczyk, et al.., Cancer Research, 57(3):466-71, February 1, 1997. Modified, nonneurovirulent herpes simplex viruses (HSVs) have shown promise in treatment of brain tumors. However, HSV-1 can infect and cause disintegration of a wide variety of cell types. HSV-1716, a mutant of the virus lacking both copies of the gene coding ICP-34.5, can effectively treat a localized intraperitoneal malignancy. Human malignant mesothelioma cells supported the growth of HSV-1716 and efficiently disintegrated in vitro. Intraperitoneal injection of HSV-1716 into animals with established tumor nodules reduced tumor burden and significantly prolonged survival in an animal model of non-central nervous system-localized human malignancy, without dissemination or persistence, after intraperitoneal injection into mice bearing human tumors. These findings suggest that this virus may be efficacious and safe for use in localized human malignancies of non-neural origin such as malignant mesothelioma. "Use of a 'replication-restricted' herpes virus to treat experimental human malignant mesothelioma", Kucharczyk, et al.., Cancer Research, 57(3):466-71, February 1, 1997.
Potential "Suicide" Gene Therapy For Malignant Mesothelioma
Replication -defective adenovirus vectors were generated in which the gene of interest B lacZ, luciferase or herpes simplex virus thymidine kinase (HSV-tk) B is driven by the adenovirus major late promoter (MLP) or the human cytomegalovirus immediate-early gene promoter/enhancer (CMV). In vitro experiments with rat and human mesothelioma cell lines revealed that the CMV promoter was stronger than the MLP promoter regarding levels of expression of the luciferase reporter gene and ganciclovir (GCV) killing efficiency after tk gene transfer. Following administration of lacZ recombinant adenovirus into the pleural cavity of rats with established mesothelioma, a widespread distribution of infectious virus particles through the thorax contents was demonstrated. However, a relatively small proportion of tumor cells were transduced. Nevertheless, a strong growth inhibition was observed following treatment with recombinant tk adenovirus and GCV. In a survival study, animals were treated with recombinant tk adenovirus and a 14 days course of GCV. This treatment prolonged symptom-free survival time from 19 days in the controls to 33 days in the treated group. These responses can be best explained by assuming continued tk expression in or around the tumor tissue during GCV treatment. These results confirm and extend earlier findings with the same model and demonstrate the potential of the herpes simplex virus thymidine kinase suicide gene therapy as a local treatment for malignant mesothelioma. "Gene therapy of experimental malignant mesothelioma using adenovirus vectors encoding the HSV-tk gene", Esandi, et al.,Gene Therapy, 5(4):280-7, April, 1997.