抗感染抗体.ppt
抗感染单抗药物抗感染单抗药物研究与开发研究与开发免疫系统是人体健康的防线，用以抵御细菌和其他微生物的侵袭，其中免疫球蛋白（抗体）在免疫保护中发挥重要作用。机体在病毒和细菌感染中以及感染后都将产生特异性抗体，该抗体可以与刺激它们产生的抗原决定簇发生特异性反应，具有重要的抗感染作用。Active immunization.Traditional vaccines work by exposing patients to immunogens from infectious agents,prompting their immune systems to produce a range of anti-pathogen(polyclonal)antibodies.This approach is ideal for healthy populations,but works less well in immunocompromised patients or in patients whose infections take hold before the vaccine has a chance to work.Passive immunization.Polyclonal antibodies or mAbs are infused directly into patients blood,where they bind to the pathogen and render it harmless by activating complement,encouraging phagocytosis,or inducing other mechanisms of antibody-mediated immunity.The antibodies can be administered both to people who are likely to be exposed to a pathogen as well as to patients with active infections.Though passive immunization generally uses preparations of polyclonal antibodies collected from human volunteers,monoclonal antibodies should(theoretically)work.Antibody therapy against bacteria can be brought about in two distinct waysNATURE BIOTECHNOLOGY 2006年代年代获奖者获奖者 获奖原因获奖原因1901Ilya Ilyich Mechnikov（俄）（俄）埃米尔埃米尔阿道夫阿道夫冯冯贝林（德）贝林（德）利用血清疗法治疗白喉利用血清疗法治疗白喉1908Paul Ehrlich（德）（德）关于免疫方面的研究关于免疫方面的研究1972杰拉尔德杰拉尔德埃德尔曼（美）埃德尔曼（美）Rodney R.Porter（英）（英）发现抗体的化学结构发现抗体的化学结构1984尼尔斯尼尔斯杰尼（丹麦）杰尼（丹麦）乔治乔治科勒（德）科勒（德）关于免疫控制机制理论关于免疫控制机制理论色萨色萨米尔斯坦（英）米尔斯坦（英）及开发制备单克隆抗体及开发制备单克隆抗体抗体研究与诺贝尔生理学和医学奖抗体研究与诺贝尔生理学和医学奖“The Pharmacy of the Future 1901”Vaccine 27S(2009)排名排名产品名产品名类别类别销售额销售额(亿亿$)1Lipitor小分子药物小分子药物133.82Plavix小分子药物小分子药物94.63Advair小分子药物小分子药物76.74Enbrel重组蛋白重组蛋白76.75Remicade单克隆抗体单克隆抗体62.56Diovan小分子药物小分子药物57.47Rituxan单克隆抗体单克隆抗体54.88Nexium小分子药物小分子药物52.09Avastin单克隆抗体单克隆抗体48.110Herceptin单克隆抗体单克隆抗体47.12008年统计全球排名前十大药品年统计全球排名前十大药品排名排名产品名产品名类别类别销售额销售额(亿亿$)1Avastin单克隆抗体单克隆抗体92.32Humira单克隆抗体单克隆抗体91.33Rituxan单克隆抗体单克隆抗体78.24Enbrel重组蛋白重组蛋白65.85Lantus重组蛋白重组蛋白63.96Herceptin单克隆抗体单克隆抗体58.07Crestor小分子药物小分子药物57.48Spiriva小分子药物小分子药物55.59Remicade单克隆抗体单克隆抗体52.210Gleevec小分子药物小分子药物51.4预计预计2014年全球排名前十大药品年全球排名前十大药品美国美国FDA已经批准或即将批准的治疗性抗体药物已经批准或即将批准的治疗性抗体药物年份年份学名学名/商品名商品名特点特点靶分子靶分子用途用途1986Muromomab/Orthoclone鼠源抗体鼠源抗体CD3抗移植排斥反应抗移植排斥反应1994Abciximab/ReoPro嵌合抗体嵌合抗体GP IIb/IIIa经经皮皮穿穿刺刺冠冠状状动动脉脉成成形形术术，心心绞绞痛痛1997Rituximab/Rituxan嵌合抗体嵌合抗体CD20B细细胞胞非非何何杰杰金金淋淋巴巴瘤瘤，慢慢性性淋淋巴细胞白血病（巴细胞白血病（2010）1997Daclizumab/Zenapax人源化抗体人源化抗体CD25移植排斥移植排斥1998Basiliximab/Simulect嵌合抗体嵌合抗体CD25移植排斥移植排斥1998Palivizuma/Synagis人源化抗体人源化抗体RSV婴幼儿呼吸道合胞病毒婴幼儿呼吸道合胞病毒1998Infliximab/Remicade嵌合抗体嵌合抗体TNF-a a溃疡性结肠炎，类风湿性关节炎溃疡性结肠炎，类风湿性关节炎1998Trastuzumab/Herceptin人源化抗体人源化抗体HER2乳腺癌，乳腺癌，HER2+胃癌（胃癌（2010）2000Gemtuzumab/Mylotarg人源化抗体人源化抗体CD33急性复发性髓性白血病急性复发性髓性白血病2001Alemtuzumab/Campath人源化抗体人源化抗体CD52难治性慢性淋巴细胞白血病难治性慢性淋巴细胞白血病2002Ibritomomab/Zevalin鼠源抗体鼠源抗体CD20难治的难治的B细胞非何杰金淋巴瘤细胞非何杰金淋巴瘤2002Adalimumab/Humira全人源抗体全人源抗体TNF-a a银屑病和银屑病关节炎银屑病和银屑病关节炎2003Omalizumab/Xolair人源化抗体人源化抗体IgE重症哮喘重症哮喘2003Tositumomab/Bexxar鼠源抗体鼠源抗体CD20B细胞淋巴瘤细胞淋巴瘤2003Efalizumab/Raptiva人源化抗体人源化抗体CD牛皮癣牛皮癣2004Cetuximab/Erbitux嵌合抗体嵌合抗体EGFR结肠直肠癌结肠直肠癌2004Bevacizumab/Avastin人源化抗体人源化抗体VEGFR结肠癌结肠癌2004Natalizumab/Tysabri人源化抗体人源化抗体整合素整合素-a a4多发性硬化病多发性硬化病2006Ranibizumab/Lucentis人源化抗体人源化抗体VEGF-A湿性老年性黄斑病湿性老年性黄斑病2006Panitumumab/Vectibix全人源抗体全人源抗体EGFR结肠直肠癌结肠直肠癌2007Eculizumab/Soliris人源化抗体人源化抗体C5蛋白蛋白阵发性夜间血红蛋白尿阵发性夜间血红蛋白尿2008Certolizumab/Cimzia人源化抗体人源化抗体TNF-a a风湿性关节炎风湿性关节炎2009Golimumab/Simponi全人全人源源抗体抗体TNF-a a类风湿和银屑病关节炎类风湿和银屑病关节炎2009Canakinumab/Ilaris全人全人源源抗体抗体IL-1b b冷吡啉相关周期性综合症冷吡啉相关周期性综合症2009Ustekinumab/Stelara全人全人源源抗体抗体IL-12,IL23成人中重度银屑病成人中重度银屑病2009Ofatumumab/Arzerra全人全人源源抗体抗体CD20难治的慢性淋巴细胞白血病难治的慢性淋巴细胞白血病2010Tocilizumab/Actemra人源化抗体人源化抗体IL-6受体受体治治疗疗无无效效的的中中重重度度类类风风湿湿性性关关节炎节炎2010Denosumab/Prolia全人全人源源抗体抗体RANKL预防绝经期后的妇女骨折预防绝经期后的妇女骨折2010Denosumab/Xgeva全人源抗体全人源抗体RANKL预防实体瘤骨转移预防实体瘤骨转移2010Raxibacumab/ABthrax 全人全人源源抗体抗体芽孢杆菌芽孢杆菌治疗吸入性炭疽病治疗吸入性炭疽病（Pending）2010Motavizumab/Numax 人源化抗体人源化抗体RSVF蛋白蛋白婴幼儿呼吸道合胞病毒婴幼儿呼吸道合胞病毒（Pending）2011Belimumab/Benlysta全人源抗体全人源抗体BLyS系统性红斑狼疮系统性红斑狼疮2011Ipilimumab/Yervoy全人源抗体全人源抗体CTLA-4晚期转移性黑色素瘤晚期转移性黑色素瘤Selected antibody therapies in clinical development against pathogensNATURE BIOTECHNOLOGY 2006脂磷壁酸转运蛋白被膜多糖聚集因子保护抗原细菌毒素Antimicrobial therapy Two phenomenons 1.drug resistance 2.host toxicityAll microbes express specific antigensThe specific antibodies are conjugated with antimicrobial drugsThe specific antibodies are conjugated with antimicrobial drugs-lower side effects,higher potency and efficacy1.reduction in the antibiotic dose2.lower side effects on the host cells3.increase in effectiveness and potency of treatment4.quick and faster onset of action plement activation 8.the enhancement of host immune functionThe antibodies conjugated to antimicrobial The antibodies conjugated to antimicrobial chemotherapy agent as antiinfective agentschemotherapy agent as antiinfective agentsMedical Hypotheses 2007Anticandidal Activities of mAb Complementarity-Determining Regions(CDRs)In vitro candidacidal activity of three different CDR peptides against Candida albicansEffect of mAb CDRs on the survival curve of mice infected intravenously with 56105 yeast cells of C.albicans白色念珠菌白色念珠菌 PLoS ONE 2008
