The researchers first tested their approach to gene therapy in test tubes, delivering genetic information to mesothelioma cells using modified viruses called retroviruses. In the past, scientists primarily used retroviruses that were unable to replicate themselves, to ensure that the replication process did not get out of control. But for their recent experiments, the Japanese team used replicable viruses – called replication-competent (RCR) viruses – instead.
While it is considered a riskier approach, using replication-competent viruses is also thought to be more effective because they can help get the key genes into more cells. This was the case in the Japanese study. The team reports that the marker gene “successfully infected and efficiently replicated” in human malignant mesothelioma cell lines in vitro without affecting non-malignant mesothelial cells.
Next, the researchers tried the same experiment in live subjects. When the replication-competent retrovirus was injected into the tumors of mesothelioma-infected mice, it showed “robust spread” and “efficient transmission” of the prodrug activator gene throughout entire tumor masses. The infected tumors were then treated with an anti-fungal drug called 5-fluorocytosine, which interferes with the building of certain essential proteins.
In a recent report of their findings in the journal Cancer Gene Therapy, the researchers say the process resulted in “significant inhibition” of tumor growth and “significantly prolonged survival” in mice with peritoneal mesothelioma. They write, “These data indicate the potential utility of RCR vector-mediated prodrug activator therapy in the treatment of malignant mesothelioma.”
Gene therapy is a promising new area of research for mesothelioma, a rare but incurable disease that is caused by exposure to the mineral asbestos. Its fast growth, drug resistance, and irregular tumor shape tend to make mesothelioma difficult to treat with conventional therapies.
Hiraoka, K, “Therapeutic efficacy of replicaion-competent retrovirus vctor-mediated suicide gene therapy in a multifocal colorectal cancer metastasis model”, June 1, 2007, Cancer Research, pp. 5345-53.