Successful engraftment of hematopoietic stem cells (HSCs) involves overcoming nonimmunologic barriers that hinder access to the HSC niches in the bone marrow (BM).1,2  Cytotoxic chemotherapy and/or radiation are currently used to reduce these barriers in clinical hematopoietic cell transplantation (HCT).1,2  Targeted and safer methods to eliminate endogenous HSCs to achieve niche clearance would substantially reduce the morbidity and mortality of an HCT. We previously showed that an anti-mouse monoclonal antibody targeting CD117, a cytokine receptor tyrosine kinase expressed on HSCs, depletes endogenous HSCs and allows donor HSC engraftment in immunodeficient mice.4-6  Signals transmitted through CD117 after interaction with its ligand, stem cell factor, are critical for HSC survival, proliferation, and differentiation.4,7 

We identified a humanized anti-human CD117 immunoglobulin G1 monoclonal antibody, AMG 191, as a candidate therapeutic antibody with the potential to...

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