Image by Robert Paulson
The cell surface molecule CD99 occurs more frequently than normal on stem cells responsible for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to research published in Science Translational Medicine.
Building on this discovery, researchers designed anti-CD99 monoclonal antibodies (mAbs).
In vitro and in vivo experiments
showed that these mAbs can recognize
and destroy AML and MDS stem/progenitor cells.
“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we show that antibodies against this target can directly kill human AML stem cells,” said study author Christopher Y. Park, MD, PhD, of NYU Langone Medical Center in New York, New York.
“While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing.”
Dr Park and his colleagues first examined stem cell populations from 79 patients with AML and 24 with MDS. More than 80% of stem cells in both groups expressed high levels of CD99.
The levels were so high that leukemia stem cells could be cleanly separated from normal hematopoietic stem cells in AML samples.
Upon confirming that CD99 was abundant on AML and MDS stem cells, the researchers made several anti-CD99 mAbs and tested them in vitro and in mouse models.
The mAbs destroyed AML and MDS stem cells by causing a sudden spike in the activity of SRC family kinases—a group of proteins that are implicated in invasion, tumor progression, and metastasis in a variety of cancers.
However, the mAbs had minimal effects on normal hematopoietic stem cells.
“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials,” Dr Park said.
