Czechowicz, A. (Agnieszka)
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- Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation(Springer Science and Business Media LLC, 2019) Wernig, G. (Gerlinde); Mansour, M.K. (Michael K.); Shizuru, J.A. (Judith A.); Scheck, A. (Amelia); Walck, E. (Emily); Palchaudhuri, R. (Rahul); Winau, F. (Florian); Hoggatt, J. (Jonathan); Pang, W.W. (Wendy W.); Tate, T.A. (Tiffany A.); Hu, Y. (Yu); Rossi, D.J. (Derrick J.); Czechowicz, A. (Agnieszka); Chan, Y.Y. (Yan Yi); Scadden, D.T (David T.); Saez, B. (Borja)Hematopoietic stem cell transplantation (HSCT) is a curative therapy for blood and immune diseases with potential for many settings beyond current standard-of-care. Broad HSCT application is currently precluded largely due to morbidity and mortality associated with genotoxic irradiation or chemotherapy conditioning. Here we show that a single dose of a CD117-antibody-drug-conjugate (CD117-ADC) to saporin leads to > 99% depletion of host HSCs, enabling rapid and efficient donor hematopoietic cell engraftment. Importantly, CD117-ADC selectively targets hematopoietic stem cells yet does not cause clinically significant side-effects. Blood counts and immune cell function are preserved following CD117-ADC treatment, with effective responses by recipients to both viral and fungal challenges. These results suggest that CD117-ADC-mediated HSCT pre-treatment could serve as a non-myeloablative conditioning strategy for the treatment of a wide range of non-malignant and malignant diseases, and might be especially suited to gene therapy and gene editing settings in which preservation of immunity is desired.