26 March 2013

Possible Treatment of Leukemia Using Monoclonal Antibodies To Target and Destroy Leukemia Cells

Leukemia Cells
Researchers have identified an antibody that specifically targets and destroys leukemia cells while ignoring normal blood cells.

Leukemia is a type of cancer that affects the blood and bone marrow. The disease causes an abnormal increase of white blood cells and causes abnormalities in the blood, the bone marrow and the lymphoid system.

Leukemia starts in the bone marrow where blood cells are produced.

The abnormal white blood cells grow faster than normal cells and does not stop growing. Over time, these leukemia cells start to crowd out the normal blood cells which results in complications such as anemia (a decrease in the number of red blood cells), bleeding, and infections. Leukemia cells can also spread to the lymph nodes or other organs and cause swelling or pain.

10% of leukemia affect newly born babies known as Infant Leukemia.

On a related note, another possible treatment for leukemia has been discovered. Memorial Sloan-Kettering researchers modified an anti-body cell with a virus that enabled it to also target and kill leukemia cells. In a clinical trial, a patient was found to be free of leukemia cells after only eight days of treatment (see embedded video).

Targeting and Destroying Leukemia Cells With Antibodies

Researchers at the University of California, San Diego Moores Cancer Center have identified a humanized monoclonal antibody that targets and directly kills chronic lymphocytic leukemia (CLL) cells.

The findings, published in the online Early Edition of the Proceedings of the National Academy of Sciences on March 25, 2013 represent a potential new therapy for treating at least some patients with CLL, the most common type of blood cancer in the United States.

CLL cells express high levels of a cell-surface glycoprotein receptor called CD44. Principal investigator Thomas Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues identified a monoclonal antibody called RG7356 that specifically targeted CD44 and was directly toxic to cancer cells, but had little effect on normal B cells.

Video: Leukemia Cure Possibly Found

Moreover, they found RG7356 induced CLL cells that expressed the protein ZAP-70 to undergo apoptosis or programmed cell death. Roughly half of CLL patients have leukemia cells that express ZAP-70. Such patients typically have a more aggressive form of the disease than patients with CLL cells that do not express that specific protein.

Previous research by Kipps and others has shown that CLL cells routinely undergo spontaneous or drug-induced cell death when removed from the body and cultured in the laboratory. They found that CLL cells receive survival signals from surrounding non-tumor cells that are present in the lymph nodes and bone marrow of patients with CLL. One of these survival signals appears to be transmitted through CD44. However, when CD44 is bound by the RG7356 monoclonal antibody, it seems to instead convey a death signal to the leukemia cell.

"By targeting CD44, it may be possible to kill CLL cells regardless of whether there are sufficient numbers of so-called 'effector cells,' which ordinarily are required by other monoclonal antibodies to kill tumor cells," said Kipps. "We plan to initiate clinical trials using this humanized anti-CD44 monoclonal antibody in the not-too-distant future."


University of California - San Diego
Proceedings of the National Academy of Sciences
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