A monoclonal antibody has been found to be directly cytotoxic to chronic lymphocytic leukemia (CLL) B cells while having little effect on normal B cells. The finding represents a potential new therapy for the treatment of CLL.
CLL cells express high levels of CD44, a cell-surface glycoprotein receptor for hyaluronic acid. A study led by Thomas J. Kipps, MD, PhD, of the University of California, San Diego (UC San Diego), Moores Cancer Center resulted in the identification of RG7356, a monoclonal antibody that specifically targets CD44. The antibody not only left normal B cells largely unaffected, but also induced programmed cell death (apoptosis) in CLL cells that expressed the protein ZAP-70.
As summarized in a statement from UC San Diego, ZAP-70 is expressed in leukemia cells in approximately half of persons with CLL. The disease is typically more aggressive in these patients than in persons with CLL cells that do not express ZAP-70.
In previous research, Kipps and colleagues discovered that CLL cells receive survival signals from surrounding non-tumor cells present in the lymph nodes and bone marrow of persons with the disease. One of these survival signals appears to be transmitted through CD44, but in the current project, described in Proceedings of the National Academy of Sciences of the United States of America (2013;110:6127-6132), CD44 bound by RG7356 seemed to instead convey a death signal.
When the investigators administered RG7356 at a concentration of 1 mg/kg to immune-deficient mice engrafted with human CLL cells, the CLL cells were completely cleared.