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 interleukin2(rIL2) was chemically modified by an active ester of polyethylene glycol (PEG5000), and the properties of modified rIL2 (PEGrIL2) were investigated after purifcation and renaturation. The effective molecular size of PEGrIL2 characterized by SDSPAGE was 25 kD. The bioactives of rIL2 and PEGrIL2 were determined by using the standard short term proliferation response measured by 3 H thymidine incorporation into CTLL2 cells.The bioactivity of PEGrIL2 decreased slightly. Activation of LAK cells by PEGrIL2 and rIL2 were compared. The cytotoxic activity of LAK cells to K562 cells and BEL7402 cells were determined by using the coloremetric LDH assay, and PEGrIL2 gave results similar to those with rIL2 alone. The pharmacokinetics of rIL2 and PEGrIL2 after intravenous injection in mice were studied. Unmodified rIL2 is cleared from plasma with half lives of 2 min and 11 min for the α and β phases. The α and β halflives of PEGrIL2 were 8 min and 142 min, respectively. Modification of rIL2 with PEG increased the β halflives as much as 12fold.For PEGrIL2 the systemic clearance rate was decreased 7.7fold from 0.165 to 0.019 ml/min. These results suggest that chemical modification of rIL2 by PEG would have a increasing antitumor potency of in lowdose administration into human, and would also markly reduce the toxic sideeffects.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
1998年第2期94-98,共5页
Chinese Journal of Immunology
关键词
白细胞介素2
化学修饰
聚乙二醇
生物学特性
rIL2 Chemical modification Polyethylene glycol LAK cells Pharmacokinetics
