Definition

An antibody-drug conjugate (ADC) consisting of a human monoclonal antibody directed against CD117 (tyrosine-protein kinase KIT; c-Kit; mast/stem cell growth factor receptor; SCFR), conjugated, via a cleavable linker, to the cytotoxic RNA polymerase II inhibitor amanitin, with potential antineoplastic activity and that can potentially be used as a conditioning agent to selectively deplete hematopoietic stem cells (HSCs) prior to allogeneic HSC transplants or other treatments for which HSCs need to be depleted. Upon administration of the anti-CD117/amanitin ADC MGTA-117, the antibody moiety targets and binds to the cell surface antigen CD117. Upon internalization and cleavage, the cytotoxic amanitin is released, binds to and inhibits RNA polymerase II. This prevents RNA synthesis and induces apoptosis of CD117-overexpressing HSCs and leukemic blasts. CD117, a transmembrane protein and receptor tyrosine kinase, is highly expressed on HSCs, progenitor cells and on leukemia cells. MGTA-117 is engineered to have a short half-life.