Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10930863 | Cytotherapy | 2012 | 10 Pages |
Abstract
Significant protection of myelo- and thrombopoiesis and up to 6-fold in vivo enrichment of CDD-transduced hematopoietic cells was observed. Enrichment was most robust early after Ara-C application and was correlated with dosage and duration of chemotherapy. Enrichment remained significant for several weeks, indicating selection at the level of a progenitor population. This notion was supported by Ara-C toxicity studies, demonstrating profound hematotoxicity and a marked delay in hematopoietic recovery, specifically in the progenitor/stem cell compartment after low/intermediate-dose Ara-C. Conclusions. These data support the concept of CDD/Ara-C as a clinically applicable in vivo selection system in hematopoietic gene therapy. The data also demonstrate marked differences in hematotoxicity between alternative Ara-C dosing schemes and suggest thorough in vivo toxicity studies to optimize further Ara-C dosing en route to safe and stable enrichment of gene-corrected hematopoiesis.
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Authors
Sebastian Brennig, Ina Rattmann, Nico Lachmann, Axel Schambach, David A. Williams, Thomas Moritz,