Mesothelioma Treatments: Gene Therapy

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Apr 24, 2009 - Mesothelioma Treatments: Gene Therapy

Mesothelioma is a rare, aggressive cancer that develops after exposure to asbestos. Approximately 2500 - 3000 cases are diagnosed per year. Asbestos exposure is the primary cause for mesothelioma, and millions of people in the United States alone have been exposed to asbestos in the workplace. Family members also get exposed when asbestos is carried home on the worker’s clothes. Many industries used asbestos as an insulating and fire retardant product:

Ship building and repair
Mining
Cement factories
Auto parts and brake repair
Construction – floor, ceiling and wall linings, pipe insulation

Environmental exposure can occur as well in areas where the air and/or soil have been contaminated by asbestos.

Mesothelioma has a short survival time, usually less than a year, and is almost always fatal. Malignant mesothelioma is more common in men, however in recent years there has been an increase in women as well. Because of a long latency period between time of exposure and development of symptoms, mesothelioma more commonly affects people in their later years of life, from 50’s through 70’s.

Traditional treatment options for mesothelioma have been a combination of surgery, chemotherapy and/or radiation therapy. These treatment modalities have shown limited results, and new therapies are constantly being explored to increase survival times and quality of life. Many researchers have dedicated themselves to studying mesothelioma in hopes of better understanding the disease and finding a cure.

Gene therapy is one alternative treatment modality being explored. Gene therapy is also referred to as molecular or biological therapy. Generally speaking gene therapy aims to replace damaged genes in cancerous cells with normal, healthy ones. Gene therapy shows promise as a novel therapeutic approach for mesothelioma treatment because of its easy accessibility of a vector-mediated gene medicine into the intrapleural cavity. Mesothelioma is localized in the lung, heart or abdominal cavities and therefore is readily accessible for taking biopsy samples or delivering genes intrapleurally. Treating the primary tumor site may lead to significant reduction in tumor size and increase survival time.

In this article, we review several studies that demonstrate that gene therapy has produced antitumor effects in mesothelioma and may be a feasible option in human clinical trials in the future.

Gene therapy research has focused on immunostimulation and using suicide gene therapy as a tumor vaccine. Experiments with gene therapy are being carried out in-vitro (Petri dishes) and in-vivo (animal models using mice and rats.) In-vivo research uses mice and rats that bear malignant tumors similar to human malignant mesothelioma. The mice are then treated with different forms of intratumoral gene transfers, which are intended to decrease tumor size or kill cancerous cells. Gene therapy research also investigates which genes are under and over-expressed and which are significantly deregulated in mesotheliomas. Studies are also exploring ways gene therapy can be used to make patients less resistant to current cancer treating drugs, which have been proven to dramatically affect survival times if not rejected by the patient.

Generally speaking, gene therapy involves injecting specially modified viruses into the pleural space (patient’s chest or abdominal cavity). The intent is that then the viruses will infect the mesothelioma cells and kill or replace them with healthy genes. Gene delivery of CD 40 ligand, followed by ganciclovir treatments, has shown promise in murine models. The ligand for CD 40 is a membrane glycoprotein on activated T cells that induce B cell proliferation and immunoglobin secretion.

Other Phase I clinical trials have studied the safety of intratumoral gene transfer of recombinant adenovirus containing herpes simplex virus thymidine kinase (HSVtk) combined with ganciclovir. Recent findings from Okayama University in Japan show that gene therapy with REIC/Dkk-3 may be a promising treatment for malignant mesothelioma. In Italy, scientists from the University of Milan have concluded that Chk1 knockdown could stop the progression of malignant cells, thereby increasing the rate of death of mesothelioma cells. The University of Western Australia has a study underway looking at the angiogenesis inhibitors SU5416, bevacizumab, and thalidomide. Other agents being studied in Phase II trials are ZD1839 and STI-571, a highly selective inhibitor of the platelet-derived growth factor receptor tyrosine kinase.

More clinical trials, as well as these mentioned, using biological and immunological techniques targeting mesothelioma are urgently needed as current treatment modalities, even when used in combination, often have unsatisfactory or limited results. Gene therapy, combined with other therapeutic modalities, may offer prolonged survival and reduced recurrence of malignant pleural mesothelioma. Collaboration between scientists and specialized centers may speed the discovery of a more effective treatment.

For more information on centers participating in clinical trials and doctors who specialize in the treatment of mesothelioma, call toll free 1-800-440-4262.

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Clapper, Patti, Schweizer & Mason

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Apr 24, 2009 - Mesothelioma Treatments: Gene Therapy

Mesothelioma Attorney | Mesothelioma Lawyers | Clapper Patti Schweizer & Mason

Mesothelioma Attorneys You Can Trust

Clapper, Patti, Schweizer & Mason

The Law Offices of Clapper, Patti, Schweizer & Mason

FREE CASE EVALUATION 1-888-855-9052

Free Informational Brochure

Apr 24, 2009 - Mesothelioma Treatments: Gene Therapy

Mesothelioma Attorney | Mesothelioma Lawyers | Clapper Patti Schweizer & Mason

Mesothelioma Attorneys You Can Trust

FREE CASE EVALUATION

1-888-855-9052