抗补体药物 LY课件.pptVIP

Complement-targeted therapeutics;Activation of the complement system;The complement system in innate and adaptive immunity;One of the most fascinating aspects of complement is the sophisticated regulation mechanism that allows a rapid reaction to pathogenic intruders while protecting host cells from its destructive potential.;The complement system is a central component of innate immunity and bridges the innate to the adaptive immune response. However, it can also turn its destructive capabilities against host cells and is involved in numerous diseases and pathological（病理） conditions. Modulation of the complement system has been recognized as a promising strategy in drug discovery, and a large number of therapeutic modalities（方式）have been developed. ;Immune surveillance functions of complement;Complement’s involvement in disease;全身 感染、败血症、超敏反应 缺血再灌注损伤（如创伤性休克、外科手术、器官移植、烧伤、冻伤和血栓等） 阵发性夜间血红蛋白尿 牛皮癣 重症肌无力 系统性红斑狼疮（SLE） 多发性硬化症 移植排斥 癌症 ;局部 中风 Alzheimer’s 病(老年痴呆) 老年性黄斑变性症 哮喘 心肌梗塞 非典型溶血尿毒综合征 Crohn’s 病 类风湿性关节炎（RA） ;Current complement therapeutics;A.丝氨酸蛋白酶抑制剂（C1r,C1s,C2a,MASP-1,MASP-2,factor D, factor B, factor I） 目前只有一种C1抑制剂浓缩剂（C1-INH）上市，用于治疗遗传性血管性水肿---C1-INH减少 B.可溶性补体调节蛋白（如sCR1） C.治疗性抗体：Eculizumab D.补体成分的抑制剂（如短肽，核酸，合成物等）（compstatin,治疗老年性黄斑变性症） E.过敏毒素受体拮抗剂（如C5a受体） 其他（如重组人MBL的替代疗法）;Regulation, deactivation and inhibition of the complement cascade on host cells by natural regulators and complement-specific therapeutics.;; 抗补体治疗是一个令人兴奋的免疫 治疗学前沿领域。不久的将来，抑制 补体将成为一种公认的临床疗法。;Steep terrain: To move a therapy from the research lab to the doctors office requires a huge investment in clinical trials, which are growing more costly and more complex every year. ;Thank you!;参考文献 1.Complement-targeted therapeutics. Nature Biotechnology. 2007, 25:1265-75. 2. Complement and its role in innate and adaptive immune responses. Cell Research. 2010, 20:34-50. 3.Complement:a key system for immune surveillance and homeostasis. Nature Immunology. 2010,11:785-97. 4.陈政良教授（南方医科大学，免疫教研室）的教学幻灯 ;美国FDA