期刊
NATURE BIOTECHNOLOGY
卷 34, 期 7, 页码 738-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.3584
关键词
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资金
- Life Science Research Foundation fellowship - Jake Wetchler Foundation
- American Society of Hematology scholar award
- NIH NHLBI [K99/R00 HL119559, HL44851, HL129903, HL107630]
- NIAID NIH [1K08AI110655]
- Gerald and Darlene Jordan Chair of Medicine of Harvard University
- Harvard Blavatnik Biomedical Accelerator Fund
Hematopoietic stem cell transplantation (HSCT) offers curative therapy for patients with hemoglobinopathies, congenital immunodeficiencies, and other conditions, possibly including AIDS. Autologous HSCT using genetically corrected cells would avoid the risk of graft-versus-host disease (GVHD), but the genotoxicity of conditioning remains a substantial barrier to the development of this approach. Here we report an internalizing immunotoxin targeting the hematopoietic-cell-restricted CD45 receptor that effectively conditions immunocompetent mice. A single dose of the immunotoxin, CD45-saporin (SAP), enabled efficient (>90%) engraftment of donor cells and full correction of a sickle-cell anemia model. In contrast to irradiation, CD45-SAP completely avoided neutropenia and anemia, spared bone marrow and thymic niches, enabling rapid recovery of T and B cells, preserved anti-fungal immunity, and had minimal overall toxicity. This non-genotoxic conditioning method may provide an attractive alternative to current conditioning regimens for HSCT in the treatment of non-malignant blood diseases.
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