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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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Autori principali: Schiedlmeier, Bernhard (Autore) , Schilz, Andrea J. (Autore) , Kühlcke, Klaus (Autore) , Maier-Laufs, Stephanie (Autore) , Baum, Christopher (Autore) , Zeller, W. Jens (Autore) , Eckert, Hans-Georg (Autore) , Frühauf, Stefan (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: January 20, 2002
In: Human gene therapy
Year: 2002, Volume: 13, Fascicolo: 2, Pages: 233-242
ISSN:1557-7422
DOI:10.1089/10430340252769761
Accesso online:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1089/10430340252769761
Verlag, lizenzpflichtig, Volltext: https://www.liebertpub.com/doi/10.1089/10430340252769761
Testo
Note sull'autore:Bernd Schiedlmeier, Andrea J. Schilz, Klaus Kühlcke, Stephanie Laufs, Christopher Baum, W. Jens Zeller, Hans-Georg Eckert, and Stefan Fruehauf
Descrizione
Riassunto: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.
Descrizione del documento:Gesehen am 20.01.2022
Descrizione fisica:Online Resource
ISSN:1557-7422
DOI:10.1089/10430340252769761

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