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ADC药物偶联技术的发展 及相关质量研究 李壮林 烟台荣昌生物工程有限公司 August13,2014 1 Globaltop10drugsin2013 2 临床上单独使用单克隆抗体的抗肿瘤的作用有限。如何增强单克隆抗 体的抗肿瘤的作用?那就是在抗体上挂上一个炸弹或称细胞毒素。 http://www.sciencedirect.com/science/article/pii/S09527915990001023 ADC(AntibodyDrugConjugate) ADCDrugs:ANovelClassofTargetedBio-Therapeutics 5 Antibody-drugconjugatetargets CurrentCancerDrugTargets,2009,9,982-1004 B.A.Teicher6 Antibody-drugconjugatetargets B.A.Teicher,CurrentCancerDrugTargets,2009,9,982-1004 7 ADCDrugsunderclinicaldevelopment Linker-Drug ADCDesignationsTargetAntigenDevelopmentTumorIndication(s)Developer Class SNG-35(Adcetris)CD30AuristatinApprovedNHL SNG-75CD70AuristatinPhaseⅠ/ⅠbRCC/NHLSeattleGenetics Anti-CD19ADCCD19Auristatin Trastuzumab-DM1Her2MaytansineApprovedHER2+BreastCaGastricCa Genentech Anti-CD22ADCCD22AuristatinPhaseⅠALL AGS-5ADCSLC44A4AuristatinPhaseⅠPancreatic,GastricCa AGS-22M6ENectin-4AuristatinPhaseⅠSolidTumorsAstellas AGS-16M8FAGS-16AuristatinPhaseⅠKidney,RCC(active,notrecruiting) PSMA-ADCPSMAAuristatinPhaseⅠ/ⅡProstateProgenics BIIB015Anti-CriptoAuristatinPhaseⅠSolidTumorBiogenIdec CDX-011GPNMBAuristatinPhaseⅠ/ⅡBreast,MelanomaCelldex CarbonicSolidTumor(active,not BAY79-4620AuristatinPhaseⅠBayer anhydrase9recruiting/terminated) BAY94-9343mesothelinMaytansinePhaseⅠSolidTumorBayer SAR3419CD19MaytansinePhaseⅠ/ⅡALL,NHL,Bcelllymphoma SAR566658CA6MaytansinePhaseⅠMalignantneoplasm(solid)Sanofi AVE9633CD33MaytansinePhaseⅠAML(terminated) BT-062CD138MaytansinePhaseⅠ/ⅡMultipleMyeloma(MM)Biotest IMGN242CanAngMaytansinePhaseⅠSolidTumor IMGN901CD56MaytansinePhaseⅠ/ⅡMM,LungCa,Ovarian,SCLC ImmunoGen IMGN388AvIntegrinMaytansinePhaseⅠSolidTumor IMGN368AvIntegrinMaytansine CMC-544CD22CalicheamicinPhaseⅠb/Ⅱ/ⅢNHL,ALL,BcelllymphomaPfizer MDX1203CD70DuocarmycinPhaseⅠRCC/NHL(suspended)BMS8 ADCDrugsApprovedbyUSAFDA DrugDrugs/AbConjugate mAb(Antigen)Drug/LinkerReducableTriggerStatus name(average)Chemistry Gemtuzumab Calicheamicinapproved(2000) Mylotargozogamicin4-6(5*)LysineYespH /Hydrazonewithdr