Mesothelioma Treatment: Gene Therapy and Cytokines

Mesothelioma Treatment

Does Immunotherapy Have a Role in Mesothelioma Treatment?

Your immune system is a series of body responses that wards off infections and diseases. Immunotherapy (or biological therapy) attempts to build up your immune system to fight cancer cells. It may involve gene therapy, monoclonal antibodies, or cytokine proteins such as interferons and interleukins.

Immunotherapy is in the experimental stage, especially for mesothelioma patients. Some research has not gone beyond the laboratory, using human and animal mesothelioma cell lines. Other studies are at the early stages of preliminary clinical trials and are not standard mesothelioma treatment.

Gene Therapy

Gene therapy means inserting specific genes into cells to change or restore their functions. In theory, the procedure may be used to block abnormal genes in cancer cells, or to repair or replace the abnormal genes. Researchers also hope to disable genes that contribute to blood vessel formation (angiogenesis) by cancer cells.

In some cases, viruses may be used to activate certain reactions within cancer cells. Using an “adenovirus” for delivery, a “suicide gene” is inserted directly into the tumor. This gene makes the cells sensitive to the toxic properties of what would otherwise be an ineffective drug such as ganciclovir. The hope is that treatment with the drug then destroys only rapidly dividing cells—i.e., the cancer cells, leaving healthy cells unharmed. Taiwanese researchers have recently used the adenovirus gene replacement method in controlling mesothelioma cell lines, obtaining encouraging results (Anticancer Res. 2003 Jan–Feb; 23(1A): 33–8). Another study considered suicide gene therapy involving the gene, keratin 19, in mesothelioma lines, making the tumor cells more sensitive to ganciclovir.

Medical researchers have also considered the role of p53 in cancer cells and normal cells. The p53 gene is a tumor suppressor gene that helps to stop cells from becoming cancerous. In many human cancers, the p53 gene is damaged. Researchers are determining ways to fix this problem, including using weakened viruses to deliver functioning p53 genes. An Italian study reported on detecting p53 abnormalities in lung cancer and mesothelioma patients (Lung Cancer. 2003 Feb; 39(2): 165–72). Abnormalities in p53 were found in a significant number of lung cancer patients, but only occasionally in mesothelioma patients. Presumably, more work will be done in this area.

Monoclonal Antibody Therapy (Passive Immunotherapy)

Antibodies are proteins made by B cells, which are types of lymphocytes or white blood cells that fight disease. Monoclonal antibodies are made in the laboratory; they derive from a single, cloned antibody–producing cell. These antibodies can recognize cancer cells. They may be used to help the immune system seek out and kill tumors, or may be combined with a chemotherapy drug, or radioactive particle. (See American Cancer Society, Monoclonal Antibody Therapy).

Some monoclonal antibodies have been used to prevent angiogenesis, the process by which cancer cells form new blood vessels so that the tumors can grow and spread. For example, bevacizumab has been used in clinical trials to fight colorectal cancer and mesothelioma. It locks into Vascular Endothelial Growth Factor (VEGF), a substance found in high levels in mesothelioma patients. One on–going clinical trial combines bevacizumab with chemotherapy drugs as a mesothelioma treatment.

Cytokines: Interferons (IFN) and Interleukins (IL)

Cytokines are proteins that occur naturally in the human body, and that are similar to hormones. They may act as messengers in the immune system, triggering the bone marrow to make more blood cells.

In 1976, Dr. Robert Gallo isolated a cytokine protein molecule called interleukin–2 (IL2). This protein is capable of stimulating the growth of immune system cells called “T–cells.” In healthy individuals, T–cells search out malignant or virally infected cells and kill them. IL2 may be used to increase the number of T–cells to combat cancers.

The Federal Drug Administration (FDA) has approved IL2 to treat renal or kidney cancer and melanoma. Using IL2 as a treatment for pleural mesothelioma is still in the experimental stages. Recent laboratory results with mesothelioma cell lines look promising. Preliminary clinical trials have shown limited success (see Lung Cancer. 2001 Jan, 31(1): 67–72; J Cell Physiol. 2000 Oct, 185(1): 126–34; and Cancer. 1998 Nov 15; 83(10): 2099–104).

Interferons are other cytokine proteins that inhibit the growth of cancer cells, as well as enhance the immune system. Some work by slowing down angiogenesis of cancer cells, or by boosting the ability of T cells to attack cancer cells.

The FDA has approved the use of interferons for melanoma, renal or kidney cancer, and for certain types of lymphoma. Interferons are being tested to see if they help increase the body’s immune response to mesothelioma.