摘要
许多单克隆抗体药物作为单一药物虽然显示出一定临床治疗效果,但其治疗效果不佳,而化疗药物疗效较强,其毒副作用也较大,如在单克隆抗体上化学偶联上小分子化学药物,是提高抗体药物疗效的重要方法之一。抗体偶联药物是由抗原特异性靶向作用的单克隆抗体和高活性细胞毒类化学药物偶联而成,是一种很有潜力的新型肿瘤治疗靶向药物。这类修饰抗体能够通过抗体部分特异性结合癌细胞表位的抗原而选择性地将高活性细胞毒药物运送到肿瘤细胞内,这将使癌症患者治疗疗效最大化,药物全身毒副作用最小化。抗体偶联药物能够协同发挥抗体的'特异性'靶向作用和高活性细胞毒类药物'高效'癌细胞杀伤作用。然而,抗体偶联药物的分子设计非常复杂,针对癌细胞不同靶点和药物适应症,需要同时充分考虑抗体、链接子和载荷药物的不同组合选择,尽管该类药物还存在诸多挑战,但最近临床研究的成功促使抗体偶联药物越来越受到极大关注和兴趣。
Although numbers of naked antibodies showing clinical efficacy as single agents,their therapeutic effect is limited.Chemotherapy is very effective but with relatively large side effects,so conjugation of small chemotherapeutic drugs to antibodies is one of the important methods to enhance therapeutic potential of antibodies.Antibody-drug conjugates(ADCs)represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies(mAbs)with the cytotoxic potency of chemotherapeutic drugs.These modified antibodies are expected to selectively deliver chemotherapeutic drugs to tumor cells and provide sustained clinical benefit to cancer patients,at the same time,minimizing systemic toxicity.ADCs are expected to bring together the benefits of highly potent drugs on the one hand and selective binders of specific tumor antigens on the other hand.However,designing an ADC is very complex,requiring thoughtful combination of antibody,linker,and payload drugs in the context of a target and a defined cancer indication.Although many challenges remain,recent clinical success has generated intense interest in this therapeutic class.
作者
宋洪彬
刘冬连
李鹏飞
赵季冬
曲妍霏
SONG Hong-bin;LIU Dong-lian;LI Peng-fei;ZHAO Ji-dong;QU Yan-fei(TOT Biopharm,Suzhou 215123,China)
出处
《药学学报》
CAS
CSCD
北大核心
2019年第10期1810-1817,共8页
Acta Pharmaceutica Sinica
