抗体靶向治疗药物课件.pptVIP

* 抗体靶向治疗药物 邵荣光 医药生物技术研究所 邵荣光，甄永苏： 抗体靶向治疗药物 见：王晓良主编. 应用分子药理学. 中国协和医科大学出版社，北京，2005 甄永苏，邵荣光主编： 抗体工程药物 化学工业出版社，北京，2002 LYMPHOCYTE HYBRIDOMA MYELOMA B淋巴细胞杂交瘤技术 Mechanism of Action: Monoclonal Ab Malignant cell Monoclonal Ab Tumor specific Ag Complement Killer leukocyte ADCC (Ab-dependent cell-mediated cytotoxicity) CDC (Complement dependent cytotoxicity) Monoclonal Ab Ligand dependent apoptosis Graphic representation of progression of monoclonal antibodies from murine to chimeric to humanized to PRIMATIZED? and human. The more human the antibody is, the less likely it will generate an immune response and the more utility it has for chronic (repeat) therapy. Generations of antibody technology 与单抗偶联的常用“弹头”药物 毒素 植物 蓖麻毒素，相思豆毒素，saporin，gelonin，modecin等 微生物 绿脓杆菌外毒素，白喉毒素 药物 抗代谢类 氨基蝶呤，MTX，Ara-C，5-FU，5-氟脱氧尿苷等 蒽环类 阿霉素，柔红霉素，去甲氧柔红霉素，吗啉阿霉素等 烷基化类 苯丙氨酸氮芥，苯丁酸氮芥，丝裂霉素C，顺铂等 抗有丝分裂 长春花碱，秋水仙碱，鬼臼毒素等 抗生素 Calicheamicin，博莱霉素，平阳霉素，力达霉素 核素 131I、125I、90Y 、67Cu 、111In 、99mTc等 Physical characteristics of some therapeutic radionuclides Monoclonal antibodies in the order of FDA-approval 2006 Panitumumab (Vectibix) GEFR Humanized IgG2k Colorectal cancer 2006 Ranibizumab (Lucentis) VEGF-A Humanized IgG1k AMD (黄斑变性） US and EU therapeutic mAb approvals to date 1, chimeric mAbs, all products (n = 39); 2, oncological chimeric mAbs (n = 21); 3, immunological chimeric mAbs (n = 9); 4, chimeric mAbs, 1987–1997 (n = 20); 5, humanized mAbs, all products (n = 102); 6, oncological humanized mAbs (n = 46); 7, immunological humanized mAbs (n = 34); 8, humanized mAbs, 1988–1997 (n = 46). Data are presented as two-year moving averages Number of therapeutic mAbs entering clinical study per year Clinical phase transition percentages for therap