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

• DOI: 10.1038/s41467-018-08201-x
• Publication Date: 2019-02-06T11:04:47Z
• Authors: Agnieszka Czechowicz; Rahul Palchaudhuri; Amelia Scheck; Yu Hu; Jonathan Hoggatt; Borja Saez; Wendy W. Pang; Michael K. Mansour; Tiffany A. Tate; Yan Yi Chan; Emily Walck; Gerlinde Wernig; Judith A. Shizuru; Florian Winau; David T. Scadden; Derrick J. Rossi
• Keywords: CD117; Hematopoietic stem cell

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.