PEGylated G-CSF (BBT-015), GM-CSF (BBT-007), and IL-11 (BBT-059) analogs enhance survival and hematopoietic cell recovery in a mouse model of the hematopoietic syndrome of the acute radiation syndrome.
PEGylated G-CSF (BBT-015), GM-CSF (BBT-007), and IL-11 (BBT-059) analogs enhance survival and hematopoietic cell recovery in a mouse model of the hematopoietic syndrome of the acute radiation syndrome.
复制标题
在急性散热综合征的造血综合征的小鼠模型中，Pegyperated G-CSF（BBT-015），GM-CSF（BBT-CSF（BBT-007）和IL-11（BBT-007）和IL-11（BBT-059）类似物增强了存活和造血细胞的恢复。
DOI：
10.1097/hp.0b013e3182a4dd4e
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发表时间：
2014-01
期刊：
影响因子：
2.2
通讯作者：
Orschell CM
中科院分区：
文献类型：
--
作者：
Plett PA;Chua HL;Sampson CH;Katz BP;Fam CM;Anderson LJ;Cox GN;Orschell CM
Hematopoietic growth factors (HGF) are recommended therapy for high dose radiation exposure, but unfavorable administration schedules requiring early and repeat dosing limit the logistical ease with which they can be used. In this report, utilizing our previously described murine model of H-ARS, survival efficacy and effect on hematopoietic recovery of unique PEGylated (PEG) HGF developed by Bolder Biotechnology (BBT) were investigated. The PEGylated-HGF possess longer half-lives and more potent hematopoietic properties than corresponding non-PEGylated-HGFs. C57BL/6 mice underwent single dose lethal irradiation (7.76–8.72 Gy, 137Cs, 0.62–1.02 Gy min−1) and were treated with various dosing regimens of 0.1, 0.3 and 1.0 mg kg−1 of analogs of humanPEG-G-CSF, murinePEG-GM-CSF, or humanPEG-IL-11. Mice were administered one of the HGF analogs at 24–28hr post irradiation, and, in some studies, additional doses given every other day (beginning with the 24–28hr dose) for a total of 3 or 9 doses. 30d survival was significantly increased with only one dose of 0.3mg kg−1 of PEG-G-CSF and PEG-IL-11, or three doses of 0.3mg kg−1 of PEG-GM-CSF (p≤0.006). Enhanced survival correlated with consistently and significantly enhanced WBC, NE, RBC, and PLT recovery for PEG-G- and PEG-GM-CSF, and enhanced RBC and PLT recovery for PEG-IL-11 (p≤0.05). Longer administration schedules or higher doses did not provide a significant additional survival benefit over the shorter, lower dose, schedules. These data demonstrate the efficacy of BBT’s PEG-HGF to provide significantly increased survival with fewer injections and lower drug doses, which may have significant economic and logistical value in the aftermath of a radiation event.
