靶向癌症治疗试剂_抗体_药物偶联物_英文.pdf

药学学报ActaPharmaceuticaSinica2009,44(9):943−952·943·

Antibody-drugconjugatesastargetedcancertherapeutics

SUNYu1,2*,YUFei1,SUNBai-wang1

(1.SchoolofChemistryandChemicalEngineering,SoutheastUniversity,Nanjing211189,China;
2.SchoolofPharmacy,JiangsuUniversity,Zhenjiang212013,China)

Abstract:Traditionalchemotherapyhasbecomeoneoftheessentialtreatmentsofcancer.However,
cytotoxicagentsarenottumorspecific,whichwouldcauseserioussideeffects.Antibody-drugconjugates
(ADCs),alsocalledimmunoconjugates,belongtothe“targetedchemotherapeutics”categoryofanti-cancerdrugs.
ADCsarecomposedofthreecomponentsincludingthecytotoxicdrug,themonoclonalantibody,andthelinker
connectingthedrugtotheantibody.Withthespecial-bindingbetweenantibodyandantigenexpressedonthe
surfaceoftargetedcancercells,ADCsprovideamethodtoachieveexcellentlocalizationofthedrugatthe
desiredsiteinthebody.TheinternalizationandformationofADCsarecrucialindesigningandapplyingan
antibodyconjugatetoaparticulardiseasemodel.Inthisreview,wesummarizethreedistinctinternalization
routesofADCsandanalysisthestructureofADCs.Wealsodiscussindetailthecategoriesandinteractionof
everycomponent,aswellastheirinfluencetotargetingproperty,liabilityandactivity.
Keywords:antibody-drugconjugate;targetedcancertherapeutics;internalization;component
CLCnumber:R916Documentcode:AArticleID:0513-4870(2009)09-0943-10

靶向癌症治疗试剂——抗体-药物偶联物

1,2*11
孙玉,于菲,孙柏旺

(1.东南大学化学化工学院,江苏南京211189;2.江苏大学药学院,江苏镇江212013)

摘要:化疗已经成为癌症治疗的一个必要手段。然而,细胞毒性试剂对肿瘤细胞缺少特异性,导致严重的副
反应。抗体-药物偶联物(ADCs),也被称为免疫偶联物,属于靶向抗癌药物的一种。抗体-药物偶联物由药物、
抗体以及偶联抗体和药物的连接键三部分组成。当抗体和癌细胞表面的抗原特异性结合时,抗体-药物偶联物即
可将药物成功靶向体内部位。抗体-药物偶联物的内在化过程和组成部分在设计和应用抗体偶联物到广泛的疾病
模型中至关重要。本文概述了抗体-药物偶联物内在化的三个途径,并对它们的结构进行了分析,详细讨论了各
个组成部分的类型、相互作用及其对抗体-药物偶联物的靶向性、稳定性和活性的影响。
关键词:抗体-药物偶联物;靶向癌症治疗;内在化;构成

Chemotherapyisanintegraltocurrentcancertherapy,Muchattentionhasbeendirectedtoselectivetargeting
becauseitiseffectiveinmanycancers,suchasacuteoftheseagentsbyconjugationtoantibodiesagainst
childhoodleukemiaandHodgkindisease.However,tumorspecifi