Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation

CD117 Hematopoietic stem cell
DOI: 10.1038/s41467-018-08201-x Publication Date: 2019-02-06T11:04:47Z
ABSTRACT
Abstract Hematopoietic stem cell transplantation (HSCT) is a curative therapy for blood and immune diseases with potential many settings beyond current standard-of-care. Broad HSCT application currently precluded largely due to morbidity mortality associated genotoxic irradiation or chemotherapy conditioning. Here we show that single dose of CD117-antibody-drug-conjugate (CD117-ADC) saporin leads > 99% depletion host HSCs, enabling rapid efficient donor hematopoietic engraftment. Importantly, CD117-ADC selectively targets cells yet does not cause clinically significant side-effects. Blood counts function are preserved following treatment, effective responses by recipients both viral fungal challenges. These results suggest CD117-ADC-mediated pre-treatment could serve as non-myeloablative conditioning strategy the treatment wide range non-malignant malignant diseases, might be especially suited gene editing in which preservation immunity desired.
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