Activated Macrophages and Rituxan™ Promising for CLL

According to results recently presented at the 43rd annual meeting of the American Society of Hematology, activated macrophages combined with Rituxan™ appear to eliminate residual cancer on the molecular level in chronic lymphocytic leukemia.

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 high quantities throughout circulating blood and in bone marrow (spongy material inside large bones that produces blood forming cells). CLL 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 a slow-growing or low-grade cancer.

Treatment of CLL may include chemotherapy, radiation, biological therapies and/or stem cell transplantation. While treatment aims to eliminate cancer altogether, often it only reduces the amount of cancer. Minimal residual disease (MRD) is the cancer remaining after a patient undergoes therapy that reduces the overall level of cancer in his/her body. It is possible that the cancer may no longer be detectable even under a microscope but may still exist at a molecular level. Cancer at this level may not produce symptoms, but is responsible for recurrences. To determine MRD in CLL, scientists use a laboratory technique known as polymerase chain reaction (PCR). PCR expands trace amounts of DNA or RNA so that the specific type of the DNA or RNA can be determined. This technique has become useful in detecting a very low concentration of residual leukemia cells, identifying the presence of one leukemia cell among 500,000 to one million non-leukemic cells.

There are few treatment options for MRD in CLL, but researchers are exploring how the body’s immune system can be bolstered to attack the remaining cancer cells. Macrophages are large and versatile immune cells that act as a microbe and cancer-devouring cells. They also stimulate other immune cells to attack cancer through immune secretions. Rituxan™ is a monoclonal antibody used to treat hematologic cancers and it has produced promising results in many clinical studies. Monoclonal antibodies are proteins that can be made in the laboratory and are designed to recognize and bind to very specific cells. Rituxan™ binds specifically to proteins on the surface of B-lymphocytes. This binding action stimulates the immune system, especially macrophages, to attack and kill the cancerous B-cells. A significant benefit of this approach is that Rituxan™ only targets cancer cells (B-cells), thus sparing healthy cells from destruction. This is in contrast to chemotherapy or radiation, neither of which differentiates between cancer cells and healthy cells in the body, a characteristic that causes potentially destructive side effects.

French researchers recently conducted a clinical trial examining whether activated macrophages armed with Rituxan™ could eliminate MRD in 10 patients with previously treated CLL that was detectable only by PCR. Macrophages collected from each patient were combined with Rituxan™ in a laboratory, then re-infused into each patient intravenously (through a vein) once a week for six consecutive weeks. Two of eight patients became cancer-free on a molecular level for 12 and 9 months, respectively. Nine of ten patients received 51 treatments in total, with no adverse treatment-related side effects occurring. These results suggest that activated macrophages combined with Rituxan™ may be effective at eradicating MRD in CLL. Individuals with CLL may wish to speak with their physician regarding the risks and benefits of this novel therapy or about participating in a clinical trial. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov) and www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (Proceedings from the 43rd American Society of Hematology, abstract #3360, Orlando, Florida, December 2001)

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