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Blood. 2019 May 9;133(19):2069-2078. doi: 10.1182/blood-2018-06-858159. Epub 2019 Feb 11.

Anti-CD117 antibody depletes normal and myelodysplastic syndrome human hematopoietic stem cells in xenografted mice.

Pang WW1,2,3,4, Czechowicz A3,4,5,6,7,8,9,10, Logan AC11, Bhardwaj R6,7,8, Poyser J2,3,4, Park CY12, Weissman IL3,4,10,13, Shizuru JA2,3,4,9.

Author information

Division of Hematology, Department of Medicine.
Division of Blood and Marrow Transplantation, Department of Medicine.
Institute for Stem Cell and Regenerative Medicine.
Stanford Cancer Institute, and.
Department of Developmental Biology, School of Medicine, Stanford University, Stanford, CA.
Department of Pathology.
Department of Clinical Laboratories, and.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA.
Department of Pathology, Stanford University Medical Center, Stanford, CA.
Division of Hematology and Blood and Marrow Transplantation, Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, CA.
Department of Pathology, School of Medicine, New York University, New York, NY; and.
Ludwig Center for Cancer Cell Research, School of Medicine, Stanford University, Stanford, CA.


The myelodysplastic syndromes (MDS) represent a group of clonal disorders that result in ineffective hematopoiesis and are associated with an increased risk of transformation into acute leukemia. MDS arises from hematopoietic stem cells (HSCs); therefore, successful elimination of MDS HSCs is an important part of any curative therapy. However, current treatment options, including allogeneic hematopoietic cell transplantation (HCT), often fail to ablate disease-initiating MDS HSCs, and thus have low curative potential and high relapse rates. Here, we demonstrate that human HSCs can be targeted and eliminated by monoclonal antibodies (mAbs) that bind cell-surface CD117 (c-Kit). We show that an anti-human CD117 mAb, SR-1, inhibits normal cord blood and bone marrow HSCs in vitro. Furthermore, SR-1 and clinical-grade humanized anti-human CD117 mAb, AMG 191, deplete normal and MDS HSCs in vivo in xenograft mouse models. Anti-CD117 mAbs also facilitate the engraftment of normal donor human HSCs in MDS xenograft mouse models, restoring normal human hematopoiesis and eradicating aggressive pathologic MDS cells. This study is the first to demonstrate that anti-human CD117 mAbs have potential as novel therapeutics to eradicate MDS HSCs and augment the curative effect of allogeneic HCT for this disease. Moreover, we establish the foundation for use of these antibody agents not only in the treatment of MDS but also for the multitude of other HSC-driven blood and immune disorders for which transplant can be disease-altering.

[Available on 2020-05-09]

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