A single dose of pegylated leridistim significantly improves neutrophil recovery in sublethally irradiated rhesus macaques

被引:22
作者
Farese, AM
Casey, DB
Vigneulle, RM
Siegel, NR
Finn, RF
Klover, JA
Smith, WG
McKearn, JP
MacVittie, TJ
机构
[1] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA
[2] Pharmacia Corp, St Louis, MO USA
关键词
leridistim; myelopoietin; myelosuppression; rhesus; neutrophil;
D O I
10.1634/stemcells.19-6-514
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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 mug/kg on day 1, while two other groups (both n = 4) received peg-leridistim at 200 mug/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.
引用
收藏
页码:514 / 521
页数:8
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