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 NATURE COMMUNICATIONS 2019; 10
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