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Multidrug resistance 1 gene transfer can confer chemoprotection to human peripheral blood progenitor cells engrafted in immunodeficient mice

Myelosuppression is the main side effect of cancer chemotherapy. An improved rate of retroviral vector-mediated gene transfer to hematopoietic stem cells, shown in more recent clinical trials, has created the basis to test the concept of myeloprotective gene therapy. We transplanted clinical-scale h...

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Main Authors: Schiedlmeier, Bernhard (Author) , Schilz, Andrea J. (Author) , Kühlcke, Klaus (Author) , Maier-Laufs, Stephanie (Author) , Baum, Christopher (Author) , Zeller, W. Jens (Author) , Eckert, Hans-Georg (Author) , Frühauf, Stefan (Author)
Format: Article (Journal)
Language:English
Published: January 20, 2002
In: Human gene therapy
Year: 2002, Volume: 13, Issue: 2, Pages: 233-242
ISSN:1557-7422
DOI:10.1089/10430340252769761
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1089/10430340252769761
Verlag, lizenzpflichtig, Volltext: https://www.liebertpub.com/doi/10.1089/10430340252769761
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Author Notes:Bernd Schiedlmeier, Andrea J. Schilz, Klaus Kühlcke, Stephanie Laufs, Christopher Baum, W. Jens Zeller, Hans-Georg Eckert, and Stefan Fruehauf
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Summary:Myelosuppression is the main side effect of cancer chemotherapy. An improved rate of retroviral vector-mediated gene transfer to hematopoietic stem cells, shown in more recent clinical trials, has created the basis to test the concept of myeloprotective gene therapy. We transplanted clinical-scale human peripheral blood progenitor cell grafts (n = 2) transduced with retroviral vector SF91m3, which contains the human multidrug resistance 1 gene (MDR1), into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Engrafted mice of one cohort were protected from paclitaxel toxicity (p < 0.05) and we noted a similar trend in the second cohort. In paclitaxel-treated mice that had received gene-transduced cells we found a significant increase in gene marking (p < 0.05 - p < 0.01) or P-glycoprotein expression (p < 0.01) compared with their chemotherapy-naive counterparts. This is the first report showing that cytostatic drug resistance gene therapy can mediate chemoprotection of human clinically relevant stem cell populations with marrow engraftment potential.
Item Description:Gesehen am 20.01.2022
Physical Description:Online Resource
ISSN:1557-7422
DOI:10.1089/10430340252769761

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