Antibody may stop leukemia early: molecular approach shows promise against blood cancer.
A new drug can halt budding leukemia in mice by binding to a key protein on the surface of blood cells predisposed to becoming cancerous, researchers report in the July 2 Cell Stem Cell.
This and other studies have paved the way for preliminary testing of a version of the drug for people with acute myeloid leukemia, a particularly lethal form of blood cancer.
The promising drug is an antibody that blocks a receptor called CD123 found on the surface of stem cells at risk of developing into leukemia cells. Normal blood stem cells serve as the templates for blood cells and various immune cells, but aberrant versions may fail to develop properly and result in leukemia.
Earlier studies have shown that leukemia stem cells are loaded with CD123, whereas normal blood stem cells have little or none of it, says study coauthor John E. Dick, a molecular biologist at the University of Toronto.
CD123 serves as a receptor for a signaling protein called interleukin-3. When interleukin-3 binds to CD123 on an aberrant cell, the linkup tilts the cell's path toward proliferation, ultimately causing acute myeloid leukemia.
To intervene in this cycle, Australian researchers working with a mouse model of leukemia devised an anti body, called 7G3. Dick teamed with the Australians to analyze the antibody's effectiveness in lab dishes of normal and aberrant blood stem cells obtained from people with leukemia. These tests showed that the antibody specifically targeted the leukemia stem cells, blocking interleukin-3 binding and preventing replication. The antibody had little effect on normal blood stem cells.
Tests on mice implanted with human leukemia stem cells showed that antibody-treated animals survived on average for 24 weeks, compared with 12 weeks for mice not getting the drug. Treated mice also showed less evidence of leukemia stem cells migrating to bone marrow, necessary for the development of full-blown leukemia. In general, the authors note, the antibody worked best when given early in the disease.
These findings, along with previous work, "suggest that the targeting of CD123 is a strategy clinically relevant and with a potentially acceptable safety profile," says Ugo Testa of the Italian National Institute of Health in Rome.
The Australian team has started treating leukemia patients with a synthetic version of the drug that caused no ill effects when tested in monkeys.
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|Title Annotation:||Body & Brain; CD123|
|Date:||Aug 1, 2009|
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