抗人DR5单抗-阿霉素交联物的制备及其细胞毒作用

Preparation and cytotoxicity of anti-human DR5 monoclonal anybody-Adriamycin conjugate in vitro

目的:介绍抗人DR5单抗YM366EC-阿霉素结合物的制备及其细胞毒作用,以探讨YM366EC作为内源性导向载体的可能性。方法:采用氧化葡聚糖(Dex)T-40作为中介载体,联结抗人DR5YM366EC与阿霉素(ADR)制备交联物366EC-Dex-ADR,交联物中ADR与366EC的克分子比为71:1。经ELISA测定交联物的抗体活性大部分保持。MTT法体外测定其细胞毒性。结果:交联物对表达DR5受体的肿瘤细胞处理24小时的IC50是游离ADM的5倍,并且和肿瘤细胞DR5受体表达相关。结论:YM366EC具有良好的导向作用,结合物对肿瘤细胞有选择性杀伤作用。

Objective：To prepare the conjugates of anti-human DR5 monoclonal antibody YM366EC and adriamycin and to observe the cytotoxicity targeted drug against tumor cells in vitro.Methods：YM366EC was conjugated with adriamycin（ADR）,via oxidative dextran T-40 as the linker.The molar ratio of YM366EC to ADR was to 71∶1.The cytotoxicity of 366EC-Dex-ADR to tumor cell lines was determined by MTT assay.Results：The cytotoxicity of 366EC-Dex-ADR to tumor cells was 5-folds more than that of free ADR.Conclusion：YM366EC has targeting activity,and the conjugate with ADR are shown a selective cytotoxicity to tumor cells.