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Gene therapy

This new type of mesothelioma treatment combats the rare asbestos cancer by correcting the disease at the DNA level. During this treatment foreign genes are inserted into cells and tissue.

Two basic types of gene therapy are known:

- Knockout gene therapy: Targeting and rendering genes that induce abnormal behavior inactive.

- Replacement gene therapy: Replacing defective genes with a normal copy.

Another mesothelioma gene therapies are:

- Tumor suppressor genes

- Gene therapy and repair genes

- Oncogenes

Gene therapy is based on injecting a specially modified virus into the pleural space of the chest, where mesothelioma most commonly develops. After the injection it can infect the mesothelioma cells with a certain gene that in its turn makes the cancer sensitive to a specific drug.

Now it is not completely clear how to get the virus into the cancer cells reliably. So more and more researches are still needed before scientists will be able to use mesothelioma gene therapy as a practical mesothelioma treatment.

"Combination" Gene Therapy

Another type of treatment is combining elements of both the toxic prodrug and genetic immunopotentiation gene therapy approaches. Several trials are currently underway at the Louisiana State University Medical Center of New Orleans. This approach involves systemic administration of GCV preceding the intrapleural instillation of an allogeneic, irradiated ovarian carcinoma cell line retrovirally transfected with HSVtk (PA1-STK cells). The PA1-STK cells will migrate to areas of intrapleural tumor and in that way it can activate killing of mesothelioma cells after GCV infusion.

This bystander killing is theorized to result from the local generation of proinflammatory cytokines (tumor necrosis factor- and IL-1). They elicit an influx of cytotoxic lymphocytes producing hemorrhagic tumor necrosis passage of toxic GCV metabolites from PA1-STK cells. It can also result from passage of toxic GCV metabolites from PA1-STK cells to mesothelioma cells via gap junctions or apoptotic vesicles. This treatment alters the tumor microenvironment in mesothelioma from inhibitory to stimulatory. This alteration in its way engender an antitumor immune response.

Problems and Future Approaches

The major challenge in gene therapy for mesothelioma is optimization of gene delivery. The ability of current nonreplicating vectors to transduce all (or most) tumor cells in a localized malignancy is limited. To increase the effectiveness of gene delivery to mesothelioma cells replicating viral vectors can be used. These vectors have the capability of killing tumors by primary viral lysis and/or via delivery of therapeutic genes to cancer cells. Replication-competent adenoviruses and mutants of the herpes simplex virus type 1 may be used for this purpose.

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