Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation.
2019; 10 (1): 617
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.
View details for PubMedID 30728354
Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation
View details for DOI 10.1038/s41467-018-08202-w
View details for Web of Science ID 000457862200001
Selective HSC-Ablation Using CD117 Antibody-Drug-Conjugates Enables Safe and Effective Murine and Human Hematopoietic Stem Cell Transplantation
CELL PRESS. 2018: 23–24
View details for Web of Science ID 000435342200045
Immune Sparing Conditioning for BMT/HSCT Using Anti-Ckit Immunotoxins
ELSEVIER SCIENCE INC. 2018: S60–S61
View details for Web of Science ID 000425476000058
Completely Non-Myeloablative/Non-Lymphoablative Conditioning for BMT/HSCT Using Anti-Ckit Immunotoxins
AMER SOC HEMATOLOGY. 2016
View details for Web of Science ID 000394446806031