Researchers designed an antibody that recognises and destroys CD99-covered leukemia cells while sparing normal blood stem cells

This is a microscopic image of a leukemia cancer stem cell (Credit: Montreh Tavakkoli) with normal DNA coloured in blue. CD99, those green-coloured spots, is a protein-sugar molecule, which occurs more frequently than normal on stem cells responsible for blood cancers, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Building on this discovery, researchers from NYU Langone Medical Center and Memorial Sloan Kettering Cancer Center designed an antibody that recognises and destroys CD99-covered leukemia cells while sparing normal blood stem cells, a finding confirmed by experiments in human cells and in mice with AML cells.

Antibodies are immune system proteins that stick to a specific target. In recent years, researchers have become capable of engineering antibodies so that they target disease-related molecules.

"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," says corresponding study author, Christopher Y. Park, MD, PhD, associate professor in the Department of Pathology at NYU Langone and its Perlmutter Cancer Center.

"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," says Park.

Direct Cell Killing

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) arise from abnormal stem cells that build up in bone marrow until they interfere with normal blood cell production. Patients struggle with anemia, increased risk for infection, and bleeding.

In AML, a small group of leukemic stem cells become incapable of maturing into red or white blood cells as intended. Most leukemias respond initially to standard treatment, but relapse is common as standard treatments fail to kill leukemia stem cells, which continue to multiply.

The researchers examined stem cells from 79 AML and 24 MDS patients and they found that approximately 85% of stem cells in both groups had high levels of CD99. The levels were so high that diseased stem cells could be cleanly separated from related, normal stem cells in AML patients.

The research team then made several CD99 antibodies, and chose to focus on the one that most effectively killed those cells. Researchers found that when the study antibody attaches itself to CD99 on the surface of a cancer stem cell, it causes leukemia stem cells to die.

"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," says Park.

More information: "CD99 is a therapeutic target on disease stem cells in myeloid malignancies," Science Translational Medicine stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aaj2025

Provided by: New York University School of Medicine