Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation
| العنوان: | Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation |
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| المؤلفون: | Czechowicz, A. (Agnieszka), Palchaudhuri, R. (Rahul), Scheck, A. (Amelia), Hu, Y. (Yu), Hoggatt, J. (Jonathan), Saez, B. (Borja), Pang, W.W. (Wendy W.), Mansour, M.K. (Michael K.), Tate, T.A. (Tiffany A.), Chan, Y.Y. (Yan Yi), Walck, E. (Emily), Wernig, G. (Gerlinde), Shizuru, J.A. (Judith A.), Winau, F. (Florian), Scadden, D.T (David T.), Rossi, D.J. (Derrick J.) |
| المصدر: | Dadun. Depósito Académico Digital de la Universidad de Navarra instname |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Ciencias de la Salud::Hematología [Materias Investigacion], digestive system diseases |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::27ac089db3b5067d69d368c23ef6b8e0 https://hdl.handle.net/10171/62135 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.dedup.wf.001..27ac089db3b5067d69d368c23ef6b8e0 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |