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/ChineseJournalofBiotechnologyDecember25,2013,29(12):1880−1886©2013ChinJBiotech,AllrightsreservedReceived:May8,2013;Accepted:June20,2013Supportedby:NationalMajorScientificandTechnologicalSpecialProjectfor“SignificantNewDrugsDevelopment”(No.2012ZX09105301).Correspondingauthor:XujieDuan.Tel:+86-25-85560000-3077;E-mail:duanxujie@simcere.com(No.2012ZX09105301)2013-08-08(12):1880−1886.DuanXJ,LiuR,XuWT.Effectofcellcultureconditionsonantibodyheterogeneity.ChinJBiotech,2013,29(12):1880−1886.::EffectofcellcultureconditionsonantibodyheterogeneityXujieDuan,RuiLiu,WeitaoXu,TongRen,andHouyongLuoJiangsuSimcerePharmaceuticalGroup,Nanjing210042,Jiangsu,ChinaAbstract:Withtheadvantageofcleartargetandlittlesideeffect,antibodydrughasattractedwidelyattentionofworldwidepharmaceuticalcompanies.However,largescalemammaliancellcultureandantibodyqualityanalysisarethebottlenecksofantibodydrugindustrializationinChina.Especiallyduetothesignificanteffectofcellcultureconditionsonantibodyheterogeneity.Therefore,itisextremelyurgenttooptimizecellcultureconditionstofavorthedemandsofantibodydrugdevelopment.Thisreviewsummarizedthemostrecentadvancesintheeffectofcellcultureconditionsonantibodyquality,followedbyaddressingthekeyissuesthatmightbestrategicallyimportantfordomesticantibodydrugdevelopment.Keywords:antibody,cellculture,heterogeneity,quality,processcondition/cjb@im.ac.cn1881FDAEMA352012[1-2][3]EMAFDACFDA[4-5](1~2g/L)(3~5g/L)()11.1Y150kDa50kDa25kDa3(ComplementaritydetermingregionCDR)Fab(Antigen-bindingfragment)Fc(Crystallizablefragment)231.231)Fab2)FcFc(Antibody-dependentcell-mediatedcytotoxicityADCC)I3)Fc(Complement-dependentcytotoxicityCDC)[6]2C2.1N(N-linkedglycosylation)1)2)ISSN1000-3061CN11-1998/QChinJBiotechDecember25,2013Vol.29No.12[7-9]2.2CIgGC(K)K(0K1K2K)CDC[10-11]2.3[12]CDRFcCDRFc[6][13]pH[10]2.4[14]Bertolotti-CiarletFcγ(FcRn)FcγRIIaFcRn[15][6]2.5Chaderjian()10[16]2.6Yuk[17]3()(pH)(CO2)3.1()()/cjb@im.ac.cn1883Tachibana[18]NybergWong[19-20]UDP-N-(UDP-GlcNAc)()()[21-22]Gramer[23][24-26]Crowell[24]Pacis[27][26]BorysN-(Neu5Gc)Neu5GcNeu5Gc[28]Jenkins[29]3.23C[10]AhnEPOUDP-GlcNAcUDP-N-(UDP-GalNac)[30]BorysNeu5Ac[28]DickCCB[31]C[32]3.3pHpHMüthingpH7.4pH6.9[33]YoonpH(6.8~7.8)6840[34]pHpH(GalT)(SiaT)CO2pHGawlizek40pHGalTSiaT[35]SchmelzerMillerCO2[36](320mOsm/kg)ISSN1000-3061CN11-1998/QChinJBiotechDecember25,2013Vol.29No.12(5.32×103Pa)PacisG0FG1F[27]3.4Trummer(100)10~90[37]Chotigeat(10~90)[38]KunkelUDP-[39](ADCCCDC)[40][41-42]3.5Senger(40~200r/min)[43]3.6Pacis[27]Kaneno[44][32]ReoProRemicade3.7()(pH)[45](10000L)CO2[46]4400750/cjb@im.ac.cn1885[47-48]EMAFDAREFERENCES[1]TherapeuticmonoclonalantibodiesapprovedorinreviewintheEuropeanUnionorUnitedStates[EB/OL].[2013-04-05].[2]TOP20Best-SellingDrugsof2012[EB/OL].[2013-04-05].=2.[3]Biosimilar&FOBChina2011[EB/OL].[2013-04-05].[4]Guidelineonsimilarbiologicalmedicinalproductscontainingmonoclonalantibodies–non-clinicalandclinicalissues[EB/OL].[2013-04-09].[5]Biosimilarity[EB/OL].[2013-04-09].[6]CorreiaIR.StabilityofIgGisotypesinserum.Mabs,2010,2(3):221−232.[7]RajuTS.TerminalsugarsofFcglycansinfluenceantibodyeffectorfunctionsofIgGs.CurrOpinImmunol,2008,20(4):471−478.[8]Biowawebsite[EB/OL].[2013-04-11].[9]EurekaTherapeuticswebsite[EB/OL].[2013-04-09].[10]VlasakJ,IonescuR.Heterogeneityofmonoclonalantibodiesrevealedbycharge-sensitivemethods.CurrPharmBiotech,2008,9(6):468−481.[11]AntesB,AmonS,RizziA,etal.AnalysisoflysineclippingofahumanizedLewis-YspecificIgGantibodyanditsrelationtoFc-mediatedeffectorfunction.TechnolBiomedLifeSci,2007,852(1/2):250−256.[12]AswasDW,ParanandiMV,SchurterBT.Isoaspartateinpeptidesandproteins:formation,significance,andanalysis.PharmBiomedAnal,2000,97(2):775−790.[13]HuangL,LuJ,WroblewskiVJ,etal.InvivodeaminationcharacterizationofmonoclonalantibodybyLC/MS/MS.AnalChem,2005,77(5):1432−1439.[14]HarrisRJ.Heterogeneityofrecombinantantibodies:linkingstructuretofunction.DevBiol(Basel),2005(0),122:117−127.[15]Bertolotti-CiarletA,WangW,LownesR,etal.ImpactofmethionineonbindingofhumanIgG1toFcRnandFcγreceptors.MolImmunol,2009,46(8/9):1878−1882.[16]ChaderjianWB,ChinET,HarrisRJ,etal.Effectofcoppersulfateonperformanceofserum-freeCHOcellcultureprocessandtheleveloffreethiolintherecombinantantibodyexpressed.BiotechnolProg,2005,21(2):550−553.[17]YukIH,ZhangB,YangY,etal.Controllingglycationofrecombinantantibodyinfed-batchcellcultures.BiotechnolBioeng,2011,108(11):2600−2610.[18]TachibanaH,Ta
本文标题:细胞培养工艺条件对抗体异质性影响的研究进展-段须杰
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