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采用聚乙二醇活性酯(PEG-5000)化学修饰重组人白细胞介素-2(rIL-2)及修饰后复性制得修饰产物PEG-rIL-2。PEG-rIL-2系列研究:经SDS-PAGE和CTLL-2短期细胞培养结合3H-TdR掺入法测定,PEG-rIL-2分子量为25kD,生物活性保留69.7%;采用LDH释放法测定证实PEG-rIL-2激活的LAK细胞对人体肝癌细胞BEL-7402和K562细胞的杀伤作用和rIL-2相近甚至强于rIL-2;小鼠体内的药代动力学研究表明,经静脉给药后,PEG-rIL-2较rIL-2的系统清除率降低了7.7倍,清除相半衰期延长了12倍。提示PEG修饰rIL-2后可能改变目前肿瘤免疫法中rIL-2的剂量方案,减少其用量和不良反应。
PEG-5000 was used to chemically modify recombinant human interleukin-2 (rIL-2) and modified to produce PEG-rIL-2. PEG-rIL-2 series of studies: PEG-rIL-2 molecular weight of 25kD, biological activity retained 69.7% by SDS-PAGE and CTLL-2 short-term cell culture combined with 3H-TdR incorporation assay; LDH release assay It was confirmed that the killing effect of PEG-rIL-2-activated LAK cells on human hepatocellular carcinoma cells BEL-7402 and K562 cells is similar to or even stronger than that of rIL-2. The pharmacokinetic studies in mice showed that intravenous , The system clearance rate of PEG-rIL-2 was 7.7 times lower than that of rIL-2, and the half-life of clearing phase was 12 times longer. It is suggested that PEG modified rIL-2 might change the dosage of rIL-2 in tumor immunotherapy and reduce its dosage and adverse reactions.