期刊
BONE MARROW TRANSPLANTATION
卷 54, 期 -, 页码 749-755出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41409-019-0599-9
关键词
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资金
- French National Institute of Health and Medical Research (INSERM)
- European Research Council grant (ERC Regenerative Therapy) [269037]
- European Union FP7 grant (CELL-PID) [261387]
- European Union H2020 grant (SCIDNet) [666908]
- Imagine Institute
- Clinical Research Hospital Program (PHRC) (Ministry of Health and Social Affairs)
- INCA-Plan Cancer grant (2009-2013)
- French National Research Agency (ANR) as part of the program Investissements d'Avenir [ANR-10-IAHU-01]
- China Scholarship Council (CSC)
- INSERM-Plan Cancer fellowship
- Deutsche Forschungsgemeinschaft (DFG)
- Fund for Scientific Research Flanders (FWO Vlaanderen research projects) [G0B2913N]
- Gilead Sciences Europe Ltd
- Cell Source, Inc.
- Chorafas Institute for Scientific Exchange of the Weizmann Institute of Science
- Kiadis Pharma
- Miltenyi Biotec
- Celgene
- Centro Servizi Congressuali
- Almog Diagnostic
Prolonged T-cell immunodeficiency following HLA-incompatible hematopoietic stem cell transplantation (HSCT) represents a major obstacle hampering the more widespread use of this approach. Strategies to fasten T-cell reconstitution in this setting are highly warranted as opportunistic infections and an increased risk of relapse account for high rates of morbidity and mortality especially during early month following this type of HSCT. We have implemented a feeder free cell system based on the use of the notch ligand DL4 and cytokines allowing for the in vitro differentiation of human T-Lymphoid Progenitor cells (HTLPs) from various sources of CD34+ hematopoietic stem and precursor cells (HSPCs). Co-transplantion of human T-lymphoid progenitors (HTLPs) and non-manipulated HSPCs into immunodeficient mice successfully accelerated the reconstitution of a polyclonal T-cell repertoire. This review summarizes preclinical data on the use of T-cell progenitors for treatment of post-transplantation immunodeficiency and gives insights into the development of GMP based protocols for potential clinical applications including gene therapy approaches. Future clinical trials implementing this protocol will aim at the acceleration of immune reconstitution in different clinical settings such as SCID and leukemia patients undergoing allogeneic transplantation. Apart from pure cell-therapy approaches, the combination of DL-4 culture with gene transduction protocols will open new perspectives in terms of gene therapy applications for primary immunodeficiencies.
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