Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation
0301 basic medicine
Immunoconjugates
Science
Article
Cell Line
Mice
03 medical and health sciences
Bone Marrow
Neoplasms
Candida albicans
Animals
Humans
Bone Marrow Transplantation
Cell Death
Q
Hematopoietic Stem Cell Transplantation
Materias Investigacion::Ciencias de la Salud::Hematología
Genetic Therapy
Hematopoietic Stem Cells
Tissue Donors
3. Good health
Mice, Inbred C57BL
Proto-Oncogene Proteins c-kit
Female
:Ciencias de la Salud::Hematología [Materias Investigacion]
DOI:
10.1038/s41467-018-08201-x
Publication Date:
2019-02-06T11:04:47Z
AUTHORS (16)
ABSTRACT
AbstractHematopoietic 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.
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