小型化Endoglin抗体与阿霉素偶联物的抗肿瘤作用研究  

Antitumor Effect of Adriamycin Conjugated with Downsized Anti-Endoglin Monclonal Antibody

作　　者：李灵[1] 黄风迎[1] 黄用豪[1] 周松林[1] 郭峻莉[1] 赵焕阁[1] 谭光宏[1] 王华[1] 

机构地区：[1]海南医学院海南省热带病重点实验室,海口571101

出　　处：《四川大学学报（医学版）》2012年第3期340-343,共4页Journal of Sichuan University(Medical Sciences)

基　　金：海南省高等学校科研基金(Hjkj200746)资助

摘　　要：目的考察抗Endoglin单克隆抗体Fab片段与阿霉素(ADM)偶联物的抗肿瘤作用。方法采用异型双功能偶联剂N-羟基琥珀酰亚胺基-间-(N-马来酰亚胺基)苯甲酸酯(m-Maleimidobenzoyl-N-hydroxy-succinimide ester,MBS)为交联剂,制备Fab-ADM偶联物,以小鼠肝癌H22皮下移植瘤模型观察其在体内抑制肿瘤生长的效果。结果所得偶联物中Fab与ADM的分子比约为1∶2。动物实验中ADM(0.4mg/kg)的抑瘤率为25.00%,偶联物(0.4mg/kg,等细胞毒性剂量)的抑瘤率达到91.94%;并且较之于ADM可延长小鼠的中位生存时间。结论 Fab-ADM偶联物较ADM对小鼠肝癌H22皮下移植瘤具有更为显著的抑制作用,有望成为新型的抗肿瘤靶向药物。Objective To study the antitumor efficacy of an immunoconjugate composed of adriamycin（ADM） and downsized Fab fragment of mouse anti-Endoglin monoclonal antibody.Methods The Fab fragment of mouse anti-Endoglin monoclonal antibody was downsized and conjugated with ADM by m-Maleimidobenzoyl-N-hydroxysuccinimide ester（MBS）.The antitumor effect of the conjugate was tested in mice bearing subcutaneous injection of H22 tumor in vivo.Results The molecular ratio of Fab∶ADM in conjugate was approximately 1∶2.The Fab-ADM conjugate inhibited the growth of H22 by 91.94% on day 14 after injection at the dose of 0.4 mg/kg,much higher the inhibition rate of 25.00% by the equivalent dose of free ADM.The median survival time of the mice treated with the conjugate was longer than those treated with free ADM.The Fab-ADM conjugate was significantly more effective than free ADM in tumor suppression and life span prolongation.Conclusion Fab-ADM displayed more significant antitumor efficacy than free ADM in vivo and might be a novel candidate for cancer treatment.

关 键 词：阿霉素 小型化Endoglin单抗 免疫偶联物 抗肿瘤 

分 类 号：R73-36[医药卫生—肿瘤]