Her2抗体与MMAE偶联物的制备及生物活性研究  

Preparation and Biological Activity of Anti-Her2 Antibody-MMAE Conjugate

作　　者：佘栋宇[1] 黄嘉慧[1] 刘东晨 张途[1] 谢秋玲[1] 

机构地区：[1]暨南大学生命科学技术学院广东省生物工程药物重点实验室基因工程药物国家工程研究中心,广州510632

出　　处：《中国生物工程杂志》2015年第2期66-71,共6页China Biotechnology

基　　金：国家"十二五"重大新药创制项目(2012ZX09202-301-001);广东省战略性新兴产业核心技术攻关(2012A080800008)资助项目

摘　　要：目的:制备Her2抗体与海兔毒素MMAE的偶联物,检测该抗体-药物偶联药物(ADC)对于乳腺癌细胞的抑制作用。方法:将Her2抗体通过一个可降解的linker与小分子毒素(MMAE)连接起来,形成抗体药物偶联物(ADC)。通过细胞学试验检测Her2抗体-MMAE偶联物对于肿瘤细胞抑制、细胞凋亡和细胞周期的作用。结果:通过优化偶联条件,ADC偶联率达80%以上。肿瘤细胞生长抑制的实验显示ADC药物的IC50比单克隆抗体的IC50明显降低,作用效果更加明显。细胞凋亡和细胞周期实验结果表明,ADC药物72h诱导细胞凋亡率高达40%,单一抗体药物则仅为20%。结论:该ADC药物具有很好的抑制乳腺癌细胞的作用。Object： To prepare an antibody drug conjugate （ADC） with Her2 antibody and MMAE. And to test the effect of this ADC on growth, apoptosis and cell cycle of breast cancer cell. Method： Anti-Her2 monoclonal antibody PH was conjugated with MMAE by a linker. The effect of ADC on tumor cell was compared with Her2 antibody in vitro. Results： The conjugating rate was about 80% under the optimized condition. It was shown that this ADC has higher ability than Her2 antibody for inhibiting growth of breast cancer cells, whether with high Her2 expression or low Her2 expression. And this ADC could induced cell apoptosis up to 40 percents, while PH only to 20 percents. Conclusion： The anti-Her2 antibody-MMAE conjugate has higher activity to inhibit cancer cell than Her2 antibody.

关 键 词：Her2抗体 MMAE 偶联 ADC 制备 

分 类 号：Q819[生物学—生物工程]