A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans
A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans
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DOI：
10.1016/s0301-472x(99)00112-5
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发表时间：
1999-12-01
影响因子：
2.6
通讯作者：
Schwab, G
中科院分区：
文献类型：
--
作者：
Molineux, G;Kinstler, O;Schwab, G
粒细胞集落刺激因子(G-CSF)已被证明在预防化疗引起的中性粒细胞减少和作为外周血祖细胞的动员方面是有效的。G-CSF的作用寿命受到两种机制的限制，即从体内清除。第一个过程被认为是通过受体(受体介导的清除[RMC])主要在中性粒细胞上介导的，第二个过程可能是肾脏清除的结果。为了开发一种新型的、在体内具有持续作用时间的非格列辛(r-MET Hug-CSF)，将其与聚乙二醇组成为一种新的衍生物，命名为SD/01。这种新制剂的预期特性将包括作用时间延长，足以覆盖完整的单疗程化疗。本研究显示，SD/01在5天内维持了正常小鼠中性粒细胞数量的显著升高。中性粒细胞减少性粉尘的影响至少持续9天，同时化疗引起的中性粒细胞减少的持续时间显著缩短。正常志愿者在单次注射SD/01后9至10天内ANC高于基线水平。来自这些正常志愿者的数据还表明，CD34(+)细胞和祖细胞的动员可能发生得更及时，动员的绝对数与每天重复注射未经修饰的Filgratim的绝对数大致相同。这些数据表明，SD/01代表了一种有效的新型非格列格替姆，单次注射可持续一至两周的作用。(C)1999年国际实验血液学学会。爱思唯尔科学公司出版。
Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (receptor mediated clearance [RMC]) predominantly on neutrophils, the second process is likely the result of renal clearance. With the intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has been made by association of Filgrastim with poly(ethylene glycol). The desired properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is shown here to sustain significantly elevated neutrophil counts in hematopoietically normal mice for 5 days. In neutropenic mite effects were noted for at least 9 days, accompanying a significant reduction in the duration of chemotherapy induced neutropenia. Normal human volunteers showed higher than baseline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34(+) cells and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrastim. These data indicate that SD/01 represents an efficacious novel form of Filgrastim with actions sustained for between one and two weeks from a single injection. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.