Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure to treat hematopoietic disorders. Current bone marrow conditioning protocols create space for healthy donor stem cells by employing irradiation and/or chemotherapy, but carry severe toxicities, resulting in significant morbidity, mortality and substantial long-term complications. To develop a low-toxicity solution, we generated a bi-specific T-cell engager (BTCE) that targets CD117, an abundantly expressed receptor on hematopoietic stem and progenitor cells (HSPC) and leukemia-initiating cells (LICs). We show that the CD117×CD3 BTCE efficiently depletes in vitro and in vivo HSPCs and LICs. The CD117×CD3 BTCE was not toxic and facilitates highly efficient engraftment of human allogenic donor CD34+cells in humanized mice, thereby restoring hematopoiesis in vivo in both normal and leukemia-bearing humanized mice. We demonstrate here that a potent CD117×CD3 BTCE enables rapid HSCT in both benign and malignant conditions.

Czech Academy of Sciences Prague Czech Republic

Department of Hematology Erasmus MC Universitair Medisch Centrum Rotterdam Rotterdam The Netherlands

Department of Immunology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands

Department of Pediatric Haematology and Oncology Harbour Biomed Shanghai Co Ltd Shanghai Shanghai China

Department of Pediatric Haematology and Oncology Motol University Hospital Department of Pediatrics Prague Czech Republic

Harbour Biomed Shanghai Co Ltd Shanghai Shanghai China

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