An international team of researchers led by Dr Thomas Kipps from the University of California, San Diego, has identified a humanized monoclonal antibody that targets and directly kills chronic lymphocytic leukemia cells.
Their research, published in the Proceedings of the National Academy of Sciences, represents a potential new therapy for treating at least some patients with chronic lymphocytic leukemia cells.
These cells express high levels of a cell-surface glycoprotein receptor called CD44. The team 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.
Moreover, the team found RG7356 induced chronic lymphocytic leukemia cells that expressed the protein ZAP-70 to undergo apoptosis or programmed cell death.
Roughly half of chronic lymphocytic leukemia patients have leukemia cells that express ZAP-70. Such patients typically have a more aggressive form of the disease than patients with chronic lymphocytic leukemia cells that do not express that specific protein.
Previous research has shown that chronic lymphocytic leukemia cells routinely undergo spontaneous or drug-induced cell death when removed from the body and cultured in the lab.
The scientists found that chronic lymphocytic leukemia cells receive survival signals from surrounding non-tumor cells that are present in the lymph nodes and bone marrow of patients with chronic lymphocytic leukemia. 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 chronic lymphocytic leukemia 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,” Dr Kipps explained.
“We plan to initiate clinical trials using this humanized anti-CD44 monoclonal antibody in the not-too-distant future.”
Bibliographic information: Suping Zhang et al. Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44. PNAS, published online before print March 25, 2013; doi: 10.1073/pnas.1221841110