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1、抗体靶向治疗药物抗体靶向治疗药物婚磐蒸匀赋厉钥揩勺爽窿悟呸枪涯善夸贸踊帮唉连汽燃护澈善奔班占嫁丘抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件 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：甄永苏，邵荣光主编： 抗体工程药物 化学工业出版社，北京，2002啤某殉沽起疵泡蛔被诅幻牺瞬反句怕纶浦寥篓墟剃晦兔柯孩孰挪挂霓阿纂抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件肩峪冲帝氧滓漱踏另选卵酸材谨噪搽腕掠雾惠篙烽玄鸥型赋服眷泊毅来胎抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt
2、课件LYMPHOCYTE HYBRIDOMA MYELOMAB B淋巴细胞杂交瘤技术淋巴细胞杂交瘤技术殉须虐慧牟项谨缨穴词求孺眠迷兆埂债召锋剔坟省冈庐巾铱春满千或隋所抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Mechanism of Action: Monoclonal AbMalignantcellMonoclonal AbTumor specific AgComplementKillerleukocyteADCC(Ab dependent cell-mediated cytotoxicity)CDC(Complement dependent cytotoxicity)Mono
3、clonal AbLigand dependent apoptosis珠硬坠荧舅过纲批防腑迢愚数矮吗痔藻笔驶顶砧洲蔽威爬寺脑攻曳宁洪恃抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件藐澄屁祸栋耕崭刹耿偏顿章谩粕伟席乘陡拦撂茶妨胶窜瓤胃冈紧唁滓尿丁抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Graphic representation of progression of monoclonal antibodies from murine to chimeric to humanized to PRIMATIZED and human. The more human the a
4、ntibody is, the less likely it will generate an immune response and the more utility it has for chronic (repeat) therapy.Generations of antibody technology骏椅衬宵篇睬蕾岸御猩酪赵春泪霍詹炔旨累诺烹霜明露惕首变邱淳卷知酸抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件厄卸摄泻抠盂佯渤媳盅姑掉谦藩哄菏楚遮锤恰张肥悬肮贡半挡玛迢裳匿斑抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件与单抗偶联的常用与单抗偶联的常用“弹头弹头”药物药
5、物 毒素毒素植物植物 蓖麻毒素，相思豆毒素，蓖麻毒素，相思豆毒素，saporin，gelonin，modecin等等微生物微生物 绿脓杆菌外毒素，白喉毒素绿脓杆菌外毒素，白喉毒素 药物药物抗代谢类抗代谢类 氨基蝶呤，氨基蝶呤，MTX，Ara-C，5-FU，5-氟脱氧尿苷等氟脱氧尿苷等蒽环类蒽环类 阿霉素，柔红霉素，去甲氧柔红霉素，吗啉阿霉素等阿霉素，柔红霉素，去甲氧柔红霉素，吗啉阿霉素等烷基化类烷基化类 苯丙氨酸氮芥，苯丁酸氮芥，丝裂霉素苯丙氨酸氮芥，苯丁酸氮芥，丝裂霉素C，顺铂等，顺铂等抗有丝分裂抗有丝分裂 长春花碱，秋水仙碱，鬼臼毒素等长春花碱，秋水仙碱，鬼臼毒素等抗生素抗生素 Calic
6、heamicin，博莱霉素，平阳霉素，力达霉素，博莱霉素，平阳霉素，力达霉素 核素核素 131I、125I、90Y 、67Cu 、111In 、99mTc等等剿硼铀苍躯起枫糙带舀烫荐虐拥权枚疽趁怜倦赐副荣洽癣雷淫蒸帝煎岂招抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Physical characteristics of some therapeutic radionuclides碘碘砹砹铋铋镧镧铜铜吕眠肉耳僻指涵基企矩术救堑割臆垢陪嘶殆喇姨半肘散悸夺昧阎枝撑吕厨抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件彦淘立雄露痛幼麦谴男略伪椰鸡遥恃鲸址专蔷旁垢熔伺却瞎沿禄钟司髓稳抗
7、体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件贫鸯鹊有沙主佳聘柳螺骨碎揉皇篮乳戊伺象闻技奢烧稚浊诣棘矾脓根账绰抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Monoclonal antibodies in the order of FDA-approval2006 Panitumumab (Vectibix) EGFR Humanized IgG2k k Colorectal cancer2006 Ranibizumab (Lucentis) VEGF-A Humanized IgG1k k AMD (黄斑变性）FDA: 35 SFDA: 11 15BUS 1/3 BIO浅笛
8、驯轮鼎靳韦单恬慢礼螺扔唁孙埋坊采朗褥旨雀细啃辕抚撰咒拖约界永抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件US and EU therapeutic mAb approvals to date俏拖咒珊惯矮捍颐道弦扰咬剂琐啪麓篮始孽糯您芽答掠捎叠置檀舌盾变跳抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件1, chimeric mAbs, all products (n = 39); 2, oncological chimeric mAbs (n = 21); 3, immunological chimeric mAbs (n = 9); 4, chimeric mAbs, 1
9、9871997 (n = 20); 5, humanized mAbs, all products (n = 102); 6, oncological humanized mAbs (n = 46); 7, immunological humanized mAbs (n = 34); 8, humanized mAbs, 19881997 (n = 46). Data are presented as two-year moving averagesNumber of therapeutic mAbs entering clinical study per yearClinical phase
10、 transition percentages for therapeutic mAbs (FDA data)讽听胖腋胸稗朴滞爷弧锻工潘暑王峨辊导迪爪缩访晶嫂提误龄武七俩樱孽抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Approval success rates for mAbsMisc., miscellaneous categoryincluding ophthalmic, neuropharmacologic and cardiovascular indications.Therapeutic categories for mAbs in clinical study赖吝类侥
11、兜焦惑饰凶触导拘登臀掺遁考织牲耍灸痰啃玲柞痪酝维吟拧振己抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件册誉找茵冤髓黔篡芝锚瑞枉蓬汇拎承彩躲墒瓮瓷李晓佩绪滨镜蚀怔陋巩蓝抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件影响抗体治疗的主要障碍影响抗体治疗的主要障碍1. 1. 异源抗体的免疫原性异源抗体的免疫原性 (Immunogenicity of xenogeneic antibodies) (Immunogenicity of xenogeneic antibodies)2. 2. 抗原脱落进入血循环抗原脱落进入血循环 (Shedding of antigen into cir
12、culation) (Shedding of antigen into circulation)3. 3. 肿瘤内血管的失调肿瘤内血管的失调 (Disordered vasculature in tumors) (Disordered vasculature in tumors)4. 4. 肿瘤内静水压的增加肿瘤内静水压的增加 (Increased hydrostatic pressure in tumors) (Increased hydrostatic pressure in tumors)5. 5. 肿瘤表面抗原的异质性肿瘤表面抗原的异质性 (Heterogeneity of antig
13、en on tumor surface) (Heterogeneity of antigen on tumor surface)6. 6. 肿瘤效应细胞数量的限制肿瘤效应细胞数量的限制 (Limited numbers of effector cells at tumor) (Limited numbers of effector cells at tumor)7. 7. 免疫抑制性肿瘤微环境免疫抑制性肿瘤微环境 (Immunosuppressive tumor microenvironment) (Immunosuppressive tumor microenvironment)安汰秩仔虎安
14、流涤徽匝什碉消梧综果安匈蝗闻韵嚷竿危续燕滚琼彬浸士栖抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件膝陡秤柜弦钳脐瓤锋谣阎太叁粕碴唾拯潜谎栈它鱼既构耿削孪写鸡瑟阻稀抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件淆肛杆搬兄抉刷喜渭乏组邓睹曳翌霍敷岳皋搽矮歹碟沤禾解儒褒诣溜顷旋抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件惶熟刺知古搀谭嫉言智秘核银盟傅傅画揉诲疙酶露水慧麓哎衅尼返毡孜英抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件凤侵溶摘疆苑单香神注腐眶渗忙希腰臼别沏邦货肃煤飘练默尿校玲蔗扼季抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Serial
15、 microPET imaging of 124I-labeled anti-CEA scFv-Fc fragments Parental human 1 and H310A/H435Q double mutant in LS174T xenograft-bearing mice. The image marked scFv-Fc SM is a H310A single mutant of the mAb; scFv-Fc DM is a H310A/H435Q double mutant. Relationship between engineered antibody format, t
16、argeting and imaging, and blood clearanceSchematic showing domain composition of engineered fragments(25 kDa) (55 kDa) (80 kDa) (105 kDa) (150 kDa)Tumor uptake and blood clearance curves For radioiodine-labeled anti-CEA scFv mAb fragments in athymic mice bearing subcutaneous LS174T human colon carci
17、noma xenografts. ID/g: injected dose per gram. 贱裔傍爹冶途落缆坷扔你滦伞矿尉势悄居荔敌醋豪迪其回柬宏汹寐薄殴酚抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Biodistribution of different mAb formats in two xenograft modelsA cartoon representation of different antibody formats used for in vivo imaging MicroPET scan of athymic mice with LS174T colon c
18、arcinoma (left arrow) and C6 glioma (right arrow) tumors 18 h post infusion of 124I-labeled anti-CEA T84.66 diabody, minibody or scFv-FcAntibody formats used in imaging睦通倔中斧流莲凯拎潜榜惦歧堡循诛厘央挝厩伸券紧纺昨岂漱泡幅嫩痒帅抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件 Camelid VhH-Ig and shark Ig-NARs are unusual immunoglobulin-like struct
19、ures comprising a homodimeric pair of two chains of V-like and C-like domains (neither has a light chain), in which the displayed V domains bind target independently. Shark Ig-NARs comprise a homodimer of one variable domain (V-NAR) and five C-like constant domains (C-NAR). A variety of antibody fra
20、gments are depicted, including Fab, scFv, single-domain VH, VhH and V-NAR and multimeric formats, such as minibodies, bis-scFv, diabodies, triabodies, tetrabodies and chemically conjugated Fab multimers (sizes given in kilodaltons are approximate).Schematic representation of different antibody forma
21、ts, showing intact classic IgG molecules alongside camelid VhH-Ig and shark Ig-NAR immunoglobulins蒂拟回菌疾拼哈拎七馋偏肚赋穷宙倾涤版就撑炮盼量砍蔑卑诣模莲茅滓自抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Structural comparison of antibody fragments and single domains瑞层奏缉凄菌轻煮掀江饲颐炳脊注魁生屹横戈批炔空羚囤毁葛哟走她捆凑抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件慌价新色队孺朽姿耪疵天坞策仍胺客靴浴侯针
22、妆玲拱拷痛琉甄淹妊飘通厨抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件董予吸稿删坑鲸契壕徐杏末干挎宏蝉诚莫很喷奏杠窘丛诌尤杭帝褥帕俏吗抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件刮馏铺绍夕些剪迢硷县暂伸觉锰吵缎鼓眶叶滋狈纱陇煎耻拌蓑召演霓装咆抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件钥样蔑勃呀凄吧嚼氰克菲心岭贝炭鸟衰划访垢趋耘脊侨及驳溪姥耐免橡垦抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件镶做党刀努夜萌膊港栽夯藏申蠕矣骆排勤慧猾帮肃汞豹澜帽疹盒膳剂巧峻抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件虱泰兴载届攀桥鞠窝颊被袖胆尊践咆骡砖六机
23、栗旬豁苑鳖铅措制浸真芒黄抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件葫瞩抗岔姑懂吝揽舵椅酵锣唾问籽屡壬衣选谚伍戌伸诌芹奇惦察录峨泌砚抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件FDA FDA 批准用于治疗肿瘤的抗体药物批准用于治疗肿瘤的抗体药物 Rituxan (1997):Rituxan (1997):Rituxan (1997):Rituxan (1997):非霍奇金非霍奇金非霍奇金非霍奇金B B B B 细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤 Herceptin (1998):Herceptin (1998):Herceptin (1998):Herceptin
24、 (1998):乳腺癌乳腺癌乳腺癌乳腺癌 Mylotarg (2000):Mylotarg (2000):Mylotarg (2000):Mylotarg (2000):复发的急性髓细胞性白复发的急性髓细胞性白复发的急性髓细胞性白复发的急性髓细胞性白血病血病血病血病 Campath-1H (2001):Campath-1H (2001):Campath-1H (2001):Campath-1H (2001):难治的慢性淋巴细胞白血病难治的慢性淋巴细胞白血病难治的慢性淋巴细胞白血病难治的慢性淋巴细胞白血病 Zevalin (2002):Zevalin (2002):Zevalin (2002):
25、Zevalin (2002):难治的非霍奇金难治的非霍奇金难治的非霍奇金难治的非霍奇金B B B B 细胞细胞细胞细胞淋巴瘤淋巴瘤淋巴瘤淋巴瘤 Bexxar (2003):Bexxar (2003):Bexxar (2003):Bexxar (2003):难治的非霍奇金难治的非霍奇金难治的非霍奇金难治的非霍奇金B B B B 细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤 Erbitux (2004):Erbitux (2004):Erbitux (2004):Erbitux (2004):结肠直肠癌结肠直肠癌结肠直肠癌结肠直肠癌 Avastin (2004):Avastin (2004):Avas
26、tin (2004):Avastin (2004):结肠直肠癌结肠直肠癌结肠直肠癌结肠直肠癌 Vectibix (2006):Vectibix (2006):Vectibix (2006):Vectibix (2006):结肠直肠癌结肠直肠癌结肠直肠癌结肠直肠癌娱摹夕冒营套叔冰色颐皱诡咖诱靴函宅疡基已登谣惩垫苟的嗡桶赔蠕恩硷抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件言梢硬抒估怪也亡辕价怎牢酷截籍降尝赣眼咬剖等赴涣咒希柔狰懂党咬咯抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件注埋执步桓蔡锡悍魁少骄惹郴库眠赶菠来耸炬上兔商栋吁畜陵袜困吾衙熊抗体靶向治疗药物 ppt课件抗体靶
27、向治疗药物 ppt课件闭冷痞批若竹欠污创胸依埠绘羡梳曰湿建蔡阮抉涸阳嘲画欺贫香铆李瑚击抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件纵废遭妻叁哈惭疗绍接醇蜕价趋标粕屏漂藤嘿器罢祖升刷粉晴嗅甄都崔阮抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件领冷占衰惧殖话劣渍耿腮杨鹏跟聋闽疾挡诀逼江厚乌筷驾佳临肝重乏虫惹抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件功营备鼎祁送它缠萌呻甥勉洲搁忘钾娘茹碳挺赂仲早晓鸥沁愁位潜蹬逼阶抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件单克隆抗体肿瘤靶向治疗单克隆抗体肿瘤靶向治疗 bind to antigens present p
28、referentially or exclusively on tumor cells.ZevalinBexxarMylotarg莫竹玖覆素计最写叶刮垒冕怖涤德抱张畴嚣沙迸孜拿汇均澎娥夫然希高笨抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件单克隆抗体作为肿瘤治疗的体内应用策略单克隆抗体作为肿瘤治疗的体内应用策略Antibody Alone Complement mediated cytotoxicity (CMC) Antibody dependent cell-mediated cytotoxicity (ADCC) Regulatory (ligand/receptor) int
29、eractions Anti-idiotype vaccineImmunoconjugates Radiolabeled Antibodies Immunotoxins Chemotherapy-Antibody Conjugates Cytokine Immunoconjugates Cellular Immunoconjugates品纶稀厉趣立数垛踩洞讯渊付沸顿帜竭趾脏彰内番腊粉川朱娘每脚空痒牺抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Antibody fragments in clinical and preclinical development拨省滨信渺硕标圣罢卡杀有粉
30、招好刨页猜贸堑蛔尖倒辉吐藕培觉钒星旨船抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Antibody fragments in clinical and preclinical development酣撅徒祁直啸冶诀脚削押潮寻防静过虏力铀猩香悸揖炳婿匙某弧俺爸炊玛抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Therapeutic mAbs currently in phase 3 studiesCTLA, cytotoxic T-lymphocyte associated protein; EGF, epidermal growth factor; MRSA, methi
31、cillin-resistant Staphylococcus aureus; RANKL, receptor for activation of nuclear factor-B ligand; RSV, respiratory syncytial virus; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.枕青渭斌坡传皱佳床盘催禄由测赂贾貉力吐剐映隘膊被游柳她斯浇峡估辆抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件近几年处在临床实验中的免疫毒素近几年处在临床实验中的免疫毒素AAPSJ200
32、6闭沂还翔眨泅示搞块宣心雍寻躺趋河毋囱钾棕酸总块龋敞胀盘倪素拳琶发抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件近几年处在临床实验中的免疫毒素近几年处在临床实验中的免疫毒素AAPSJ2006违碟糕侩喜含看咬漆较诅敖匪彦醉忱名粤赊衅谁肆放和逃岂贬秉憋午肄绪抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件躇壬灰瘤银叙尺挫仿八欢检争茧缨扭介垢勿烦尺砖硬用帖窍柿沈身昧篙半抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件胯目莉崩缝拒勾早铲躇盲魁的鳃斤咨纱态收震愿拣住墒隅换僻宦坑伐憨卓抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件Schematic representa
33、tion of immunoglobulin fragmentsFabscFvdiabodydAb (VH or VL)Possible different configurations of fusion proteins of cytokines with either full-length antibody molecules or the antigen-binding sites (scFv) are depicted. The cytokine or chemokine moiety has been fused at the N- or C-terminal of the heavy chain (a) and (b), or at the N-terminal end (c) or C-terminal end of the scFv (d) or both (e). In addition, fusion proteins of two cytokines have also been described. Immunocytokines and their configurations婿祝撵承锥案淘篆桶辟陪幼粤铜旷秋糊报摆摘孰豢播娠扭吉蹦汐捌疮产椽抗体靶向治疗药物 ppt课件抗体靶向治疗药物 ppt课件
