Mesothelioma Information & Facts Newsletter

Mesothelioma Treatment Options - Gene Therapy

Oncolink has an excellent summary of the different aspects of gene therapy for lay people.

Mesothelioma Treatment Options: Gene Therapy

Gene therapy is used in several ways to fight cancer. It can be used to boost the immune system and improve the body's natural ability to fight cancer. Gene therapy has also been used to try to make the cancer cells more sensitive to conventional treatments, such as radiation, chemotherapy or hormone therapy. Gene therapy may have the potential to replace missing or non-functioning genes. Gene therapy can create "suicide genes" that can enter cancer cells and cause them to self-destruct. Cancers require a blood supply to grow and survive, and they form their own blood vessels to accomplish this. Genes can be used to prevent these blood vessels from forming, starving the tumor to death (also called antiogenesis). Combinations of techniques called multimodality therapy, including conventional therapy (chemo- and radiotherapy, surgery) with gene therapy may be our best weapon in the fight against mesothelioma.

This a new treatment which is currently in clinical trials. Using an adenovirus for delivery, a "suicide gene" is inserted directly into the tumor. This gene makes the cells sensitive to a normally ineffective drug, such as glanciclovir. Treatment with the drug then destroys those cells that are rapidly dividing - which are the cancer cells - leaving the healthy cells unharmed.

In theory, this mesothelioma treatment option targets the tumor specifically, as opposed to treatments such as chemotherapy which also kill healthy cells. Mesothelioma may be particularly well suited for gene therapy treatment because of its accessibility, allowing both intrapleural and intratumoral gene delivery.

Four different gene therapy trials have been carried out in mesothelioma patients, using different vector systems (adenovirus, vaccinia virus, irradiated tumor cells), and different transgenes (herpes simplex virus thymidine kinase (HSVtk) combined with ganciclovir, IL-2, IFN-beta). Although small in scale, these trials have shown much promise. (Cancer Gene Ther. 2006 Oct;13(10):897-904) [abstract].

Gene therapy for mesothelioma treatment is being researched at the University of Pennsylvania, at the Thoracic Oncology Research Laboratory. This treatment is not without risk, as became apparent in the death of Jesse Gelsinger, a University of Pennsylvania gene therapy trial participant. (Note that Mr. Gelsinger was not a participant in the mesothelioma trial.) There may also be a risk of a secondary cancer developing as well.

Mesothelioma Treatment Options: Cytokines - Interferons (IFN) and Interleukins (IL):

Cytokines are small proteins that occur naturally in the human body. They are similar to hormones and have specific effects on the behavior of other cells.

In 1976 Dr. Robert Gallo (later head of the National Cancer Institute, and famous for his work on HIV) isolated a cytokine protein molecule called interleukin-2 (IL2) which is capable of stimulating the growth of immune system cells called T-cells. T-cells are sometimes called "killer cells" because they search out malignant or virally infected cells and kill them. Use of IL2 as a pleural mesothelioma treatment option is still in the experimental stages, but researchers hope that injecting IL2 intrapleurally will promote a significant anti-tumor response.

Interferons are also naturally occuring cytokine proteins, but they inhibit the growth of malignant cells as well as enhance the immune system. Like interleukins, these immune system promoters are being tested to see if they help increase the body's response to what is often an extremely resistant malignancy, mesothelioma.

A recent study phase 1 dose escalation study evaluated the safety and feasibility of single-dose intrapleural IFN-beta gene transfer using an adenoviral vector (Ad.IFN-beta) in patients with malignant pleural mesothelioma (Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4456-66) [abstract].

There were positive results, with antitumor immune responses in 7 of the 10 patients and four of 10 patients showed meaningful clinical responses.

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