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聚乙二醇衍生物修饰的IL-12制备及体外评价

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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.
Preparation and in vitro evaluation of polyethylene glycol derivatives modified IL-12
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.

PEGIL-12Hemogram recoveryAnti-tumor

刘艺、邹镇阳、李宗艳、韩峰、乔天奎、王建刚

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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

聚乙二醇 IL-12 血象恢复 抗肿瘤

国家科技重大专项山东省重大科技创新工程项目

2017ZX093030172018CXGC1404

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(7)
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