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- Title
Hematopoietic Stem and Progenitor Cell Mobilization in Mice and Humans by a First-in-Class Mirror-Image Oligonucleotide Inhibitor of CXCL12.
- Authors
Vater, A; Sahlmann, J; Kröger, N; Zöllner, S; Lioznov, M; Maasch, C; Buchner, K; Vossmeyer, D; Schwoebel, F; Purschke, W G; Vonhoff, S; Kruschinski, A; Hübel, K; Humphrey, M; Klussmann, S; Fliegert, F
- Abstract
NOX-A12 is a PEGylated mirror-image oligonucleotide (a so-called Spiegelmer) that binds to CXCL12 (stromal cell-derived factor-1, SDF-1) with high affinity thereby inhibiting CXCL12 signaling on both its receptors, CXCR4 and CXCR7. In animals, NOX-A12 mobilized white blood cells (WBCs) and hematopoietic stem and progenitor cells (HSCs) into peripheral blood (PB). In healthy volunteers, single doses of NOX-A12 had a benign safety profile and also dose-dependently mobilized WBCs and HSCs into PB. HSC peak mobilization reached a plateau at five times the baseline level at an i.v. dose of 5.4 mg/kg. In accordance with the plasma half-life of 38 h, the duration of the WBC and HSC mobilization was long lasting and increased dose-dependently to more than 4 days at the highest dose (10.8 mg/kg). In conclusion, NOX-A12 may be appropriate for therapeutic use in and beyond mobilization of HSCs, e.g., in long-lasting mobilization and chemosensitization of hematological cancer cells.
- Subjects
HEMATOPOIETIC stem cells; PROGENITOR cells; OLIGONUCLEOTIDES; POLYETHYLENE glycol; CELLULAR signal transduction; LABORATORY mice
- Publication
Clinical Pharmacology & Therapeutics, 2013, Vol 94, Issue 1, p150
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2013.58