聚乙二醇修饰重组人白细胞介素-2及其生物学特性  

CHEMICAL MODIFICATION OF RECOMBINANT HUMAN INTERLEUKIN2 AND ITS BIOLOGICAL CHARACTERIZATION

作　　者：王立夫[1] 吴裕忻[1] 乔敏敏[1] 

机构地区：[1]上海第二医科大学附属瑞金医院内科消化研究室

出　　处：《中国免疫学杂志》1998年第2期94-98,共5页Chinese Journal of Immunology

摘　　要：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。The recombinant human interleukin2(rIL2) was chemically modified by an active ester of polyethylene glycol (PEG5000), and the properties of modified rIL2 (PEGrIL2) were investigated after purifcation and renaturation. The effective molecular size of PEGrIL2 characterized by SDSPAGE was 25 kD. The bioactives of rIL2 and PEGrIL2 were determined by using the standard short term proliferation response measured by 3 H thymidine incorporation into CTLL2 cells.The bioactivity of PEGrIL2 decreased slightly. Activation of LAK cells by PEGrIL2 and rIL2 were compared. The cytotoxic activity of LAK cells to K562 cells and BEL7402 cells were determined by using the coloremetric LDH assay, and PEGrIL2 gave results similar to those with rIL2 alone. The pharmacokinetics of rIL2 and PEGrIL2 after intravenous injection in mice were studied. Unmodified rIL2 is cleared from plasma with half lives of 2 min and 11 min for the α and β phases. The α and β halflives of PEGrIL2 were 8 min and 142 min, respectively. Modification of rIL2 with PEG increased the β halflives as much as 12fold.For PEGrIL2 the systemic clearance rate was decreased 7.7fold from 0.165 to 0.019 ml/min. These results suggest that chemical modification of rIL2 by PEG would have a increasing antitumor potency of in lowdose administration into human, and would also markly reduce the toxic sideeffects.

关 键 词：白细胞介素2 化学修饰 聚乙二醇 生物学特性 

分 类 号：R979.5[医药卫生—药品]