title: Hematopoietic stem and progenitor cell mobilization in mice and humans by a first-in-class mirror-image oligonucleotide inhibitor of CXCL12.
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.
authors.affiliation: NOXXON Pharma AG, Berlin, Germany. avater@noxxon.com
authors.forename: A
authors.initials: A
authors.lastname: Vater
authors.forename: J
authors.initials: J
authors.lastname: Sahlmann
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.forename: S
authors.initials: S
authors.lastname: Zöllner
authors.forename: M
authors.initials: M
authors.lastname: Lioznov
authors.forename: C
authors.initials: C
authors.lastname: Maasch
authors.forename: K
authors.initials: K
authors.lastname: Buchner
authors.forename: D
authors.initials: D
authors.lastname: Vossmeyer
authors.forename: F
authors.initials: F
authors.lastname: Schwoebel
authors.forename: W G
authors.initials: WG
authors.lastname: Purschke
authors.forename: S
authors.initials: S
authors.lastname: Vonhoff
authors.forename: A
authors.initials: A
authors.lastname: Kruschinski
authors.forename: K
authors.initials: K
authors.lastname: Hübel
authors.forename: M
authors.initials: M
authors.lastname: Humphrey
authors.forename: S
authors.initials: S
authors.lastname: Klussmann
authors.forename: F
authors.initials: F
authors.lastname: Fliegert
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000378:metabolism*; D008251:Macaca; D008297:Male; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D009841:Oligonucleotides / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D054377:Chemokine CXCL12; D009841:Oligonucleotides