A novel gene therapy strategy has shown significant potential towards a possible breakthrough in the treatment of patients with chronic lymphocytic leukemia (CLL). Results from a recent clinical study published in the journal Blood showed a reduction in cancer following a treatment utilizing a specific gene therapy approach.
Every human being inherits their traits from their parents. Genes are chemical molecules that are responsible for transferring these traits from parent to offspring. Genes contain all of the information needed by every cell in the human body for maintenance and growth. Cancer often develops when an abnormal alteration in a gene sequence occurs, causing normal cells in the body to turn cancerous. In addition, gene alterations may disable the immune system from destroying developing cancer cells in the body. Gene therapy involves the manipulation of genes in ways that correct or override the abnormal alterations that cause cancer. This can be accomplished by replacing or inactivating a dysfunctional gene, replacing or adding a functional gene or inserting a gene into a cell to make it function normally.
Chronic lymphocytic leukemia (CLL) is a cancer involving the lymph (immune) system which includes lymph nodes, blood, and blood vessels found throughout the body, as well as the spleen, thymus, and tonsils. This cancer is found in large amounts in circulating blood and bone marrow (spongy material inside large bones that produces blood forming cells). Chronic lymphocytic leukemia is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells of which there are two types: B and T-cells. These cells are produced in the bone marrow and each has a very specific function in aiding the body to fight infection. The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal, accumulating in the blood, bone marrow, lymph nodes and spleen. This results in overcrowding of these areas, suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the ability of the body to fight infection. CLL is considered to be a slow-growing, or low-grade cancer.
The majority of patients with CLL ultimately experience a return of their cancer following standard treatment. This fact clearly demonstrates the necessity for exploring novel therapies outside the realm of standard therapies. These novel therapies could be used alone as treatment or to augment current treatments, in order to achieve a cure. Gene therapy is currently in its early stages of development and is being evaluated in early phase clinical trials as a new form of treatment for patients with cancer.
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Part of the problem with CLL is that leukemia cells do not provoke healthy immune cells to attack and/or kill them. However, when CLL cells are exposed to a specific molecule, they are stimulated to express certain proteins on their surface. These surface proteins are recognized by immune cells as “foreign”, and provoke an immune attack against the cancer cells.
In a recent clinical study, a gene therapy approach involving an immune attack on cancer cells was evaluated for treatment of patients with progressive or advanced CLL. Patients had a small percentage of their cancer cells filtered from their blood. The cancer cells were genetically altered so that they would express the surface proteins known to provoke an immune response. The cells were then infused back into the patient’s body.
The patients were divided into three groups, with each group receiving a different dosage of genetically altered cancer cells. All of the patients who received the highest doses showed a substantial decrease of cancer cells in their body. Three months following treatment, not one patient that had received the highest doses experienced disease progression. Through some unknown mechanism, leukemia cells that had not been genetically altered were also affected by this procedure. Moreover, this treatment was tolerated very well with only minimal side effects experienced by patients.
These results are promising as they show hope for the development of new treatment strategies in the treatment of CLL. Patients with CLL may wish to speak with their doctor about participating in a clinical trial utilizing this gene therapy approach or other novel treatment strategies. Two sources of ongoing information that can be discussed with a doctor include services provided by the National Cancer Institute (cancer.gov) and eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (Blood, Vol 96, No 9, pp 2917-2924, 2000)
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