Hematopoietic stem cell transplant (HSCT) is a highly effective and potentially curative treatment for malignant and non-malignant blood disorders. However, patient eligibility for this procedure can be limited due to the mortality and morbidity risks associated with current conditioning regimens, including organ toxicity, infertility, and secondary malignancies. We have developed a novel anti-CD117 antibody drug conjugate (ADC) that, in combination with lymphodepleting antibodies, can effectively condition mice to support a full allogeneic (allo) transplant. Specifically, we used a tool anti-mouse (anti-m) CD117-PBD ADC in combination with anti-mCD4 and CD8 depleting antibodies and assessed the ability of the combination to successfully condition in a murine model of allo-HSCT.