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To date, no AML\u2010exclusive, non\u2010HSPC\u2010expressed cell\u2010surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface\u2010directed immunotherapy in this disease setting, time\u2010limited combined immune\u2010targeting of AML cells and healthy HSPCs, followed by hematopoietic stem cell transplantation (HSCT), might be a viable therapeutic approach. To explore this, we generated a recombinant single\u2010chain variable fragment\u2010based bispecific T\u2010cell engaging and activating antibody directed against CD3 on T\u2010cells and CD117, the surface receptor for stem cell factor, expressed by both AML cells and healthy HSPCs. Bispecific CD117xCD3 targeting induced lysis of CD117\u2010positive healthy human HSPCs, AML cell lines and\u00a0patient\u2010derived AML blasts in the presence of T\u2010cells at subnanomolar concentrations in vitro. Furthermore, in immunocompromised mice, engrafted with human CD117\u2010expressing leukemia cells and human T\u2010cells, the bispecific molecule efficiently prevented leukemia growth in vivo. Additionally, in immunodeficient mice transplanted with healthy human HSPCs, the molecule decreased the number of CD117\u2010positive cells in vivo. Therefore, bispecific CD117xCD3 targeting might be developed clinically in order to reduce CD117\u2010expressing leukemia cells and HSPCs prior to HSCT.<\/jats:p>","DOI":"10.1002\/hem3.70055","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T09:46:20Z","timestamp":1732009580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A single\u2010chain variable fragment\u2010based bispecific T\u2010cell activating antibody against CD117 enables T\u2010cell mediated lysis of acute myeloid leukemia and hematopoietic stem and progenitor cells"],"prefix":"10.1002","volume":"8","author":[{"given":"Laura","family":"Volta","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology University and University Hospital Z\u00fcrich Z\u00fcrich Switzerland"},{"name":"Comprehensive Cancer Center Z\u00fcrich University and University Hospitals Z\u00fcrich Z\u00fcrich 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