Scientific publications

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

Feb 6, 2019 | Magazine: Nature Communications

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


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.

CITATION  Nat Commun. 2019 Feb 6;10(1):617. doi: 10.1038/s41467-018-08201-x.