聚乙二醇衍生物修饰的IL-12制备及体外评价
Preparation and in vitro evaluation of polyethylene glycol derivatives modified IL-12
刘艺 1邹镇阳 1李宗艳 1韩峰 2乔天奎 3王建刚3
作者信息
- 1. 中国海洋大学医药学院,青岛 266000;康立泰生物医药(青岛)有限公司,青岛 266000
- 2. 中国海洋大学医药学院,青岛 266000
- 3. 康立泰生物医药(青岛)有限公司,青岛 266000
- 折叠
摘要
目的:制备聚乙二醇衍生物修饰的IL-12,确定其修饰位点,并在稳定性、血象恢复、抗肿瘤等多方面对其进行体外评价.方法:使用聚乙二醇丙醛、马来酰亚胺衍生物修饰IL-12,超高效液相色谱(UPLC)确定两种不同衍生物的修饰位点;使用重组人IL-12、PEG-IL-12刺激NK92细胞,试剂盒评估IFN-γ活性及细胞毒性;刺激CD34+评估其血象恢复潜力;刺激NK细胞杀伤活力评估其在提高免疫力、抗肿瘤方面的效果.结果:与重组人IL-12相比,PEG-IL-12具有更高的稳定性、血象恢复潜能和抗肿瘤效果.结论:PEG-IL-12可有效克服重组人IL-12的诸多缺点,显著提高IL-12在临床试验中广泛应用的可能.
Abstract
Objective:To prepare IL-12 modified with polyethylene glycol derivatives and determine its modification sites,and to evaluate it in vitro in terms of stability,hemogram recovery,anti-tumor effects and other aspects.Methods:IL-12 was modified with polyethylene glycol propionaldehyde and maleimide imide derivatives,and modified sites of two different derivatives were deter-mined by ultra performance liquid chromatography(UPLC).Recombinant human IL-12 and PEG-IL-12 were used to stimulate NK92 cells,activity and cytotoxicity of IFN-γ were evaluated by kits.CD34+was stimulated to evaluate its blood picture recovery potential.NK cell killing was stimulated to evaluate its effectiveness in improving immunity and anti-tumor effects.Results:Compared with recombinant human IL-12,PEG-IL-12 had higher stability,blood picture recovery potential and anti-tumor effects.Conclusion:PEG-IL-12 can effectively overcome many drawbacks of recombinant human IL-12,greatly improving possibility of its widespread applica-tion in clinical trials.
关键词
聚乙二醇/IL-12/血象恢复/抗肿瘤Key words
PEG/IL-12/Hemogram recovery/Anti-tumor引用本文复制引用
基金项目
国家科技重大专项(2017ZX09303017)
山东省重大科技创新工程项目(2018CXGC1404)
出版年
2024
国家科技期刊平台
NSTL
万方数据