Premium
Hematopoietic Stem and Progenitor Cell Mobilization in Mice and Humans by a First‐in‐Class Mirror‐Image Oligonucleotide Inhibitor of CXCL12
Author(s) -
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
Publication year - 2013
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2013.58
Subject(s) - cxcr4 , progenitor cell , stem cell , haematopoiesis , stromal cell , mobilization , hematopoietic stem cell , stromal cell derived factor 1 , pharmacology , immunology , cancer research , medicine , receptor , biology , microbiology and biotechnology , chemokine , history , archaeology
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. Clinical Pharmacology & Therapeutics (2013); 94 1, 150–157. doi: 10.1038/clpt.2013.58