A single dose of pegylated leridistim significantly improves neutrophil recovery in sublethally irradiated rhesus macaques.
Leridistim, a member of the myelopoietin family of dual receptor agonists that binds interleukin-3 and G-CSF receptors, has been shown to enhance hematopoietic activity in rhesus monkeys above that observed with either cytokine alone or in combination. This study demonstrated the ability of a pegylated form of leridistim (peg-leridistim), administered s.c., as a single- or two-dose regimen separated by 4 or 7 days, to significantly improve neutrophil recovery following radiation-induced myelosuppression. Rhesus macaques were total body x-irradiated (250 kVp, TBI) to 600 cGy. Following TBI, two groups received peg-leridistim (n = 5) or leridistim (n = 4) at a dose of 600 microg/kg on day 1, while two other groups (both n = 4) received peg-leridistim at 200 microg/kg on day 1 and day 4, or day 1 and day 7. The irradiation controls (n = 7) received 0.1% autologous serum for 18 days. All peg-leridistim treatment schedules significantly improved all neutrophil-related parameters following TBI as compared with nontreated controls and were equivalent in effect when compared among themselves. Administration of a single high dose or two separate lower doses of peg-leridistim significantly improved neutrophil regeneration, in a manner equal to that of conventional daily or abbreviated every-other-day administration of leridistim in this nonhuman primate model of severe myelosuppression.
Farese
A M
AM
University of Maryland, Greenebaum Cancer Center, 655 West Baltimore Street, BRB 7-049, Baltimore, MD 21201, USA. afarese@umaryland.edu
Casey
D B
DB
Vigneulle
R M
RM
Siegel
N R
NR
Finn
R F
RF
Klover
J A
JA
Smith
W G
WG
McKearn
J P
JP
MacVittie
T J
TJ
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D007377:Interleukin-3 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008657:Metabolic Clearance Rate; D009503:Neutropenia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011829:Radiation Dosage; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects
D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C400711:leridistim; D011092:Polyethylene Glycols