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A Single Dose of Pegylated Leridistim Significantly Improves Neutrophil Recovery in Sublethally Irradiated Rhesus Macaques

University of Maryland, Greenebaum Cancer Center, 655 West Baltimore Street, BRB 7-049, Baltimore, MD 21201, USA.
Stem Cells (Impact Factor: 7.13). 02/2001; 19(6):514-21. DOI: 10.1634/stemcells.19-6-514
Source: PubMed

ABSTRACT 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.

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Available from: Thomas J Macvittie, Dec 11, 2014
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    • "Rhesus macaques irradiated with 6 Gy of X-rays and subsequently given the IL-3 and granulocyte colony-stimulating factor (G-CSF) receptor agonists leridistim and pegylated leridistim, showed significant improvement of all neutrophil-related parameters when compared to the non-irradiated controls (Farese et al., 2001). This indicated recovery from severe myelosuppression (Farese et al., 2001). Future studies may reveal additional cytokines that will further increase the effectiveness of this treatment in order to optimize protection and accelerate the recovery of irradiated organisms. "
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    • "n radiation myelosuppressed non - human primates better than IL - 3 or G - CSF ( Farese et al . , 2001b ) . The administration of a single high dose of pegylated leridistim significantly improved neutrophil regeneration , in a manner equal to that of conventional daily or every other day administration of leridistim in non - human primate models ( Farese et al . , 2001c ) . Progenipoietin combines Flt - 3 ( an early acting hemato - poietic cytokine ) and G - CSF ligands , and activates cells bearing Flt - 3 and G - CSF surface receptors ( Fry et al . , 2002 ; Streeter et al . , 2001 ) . The preclinical data indicate that the chimeric growth factor receptor agonists are potent stim - ulators of hematopo"
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