Generation of Monoclonal Antibodies against Highly Conserved Antigens 英文参考文献.docVIP

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Generation of Monoclonal Antibodies against Highly Conserved Antigens 英文参考文献.doc

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Generation of Monoclonal Antibodies against Highly Conserved Antigens 英文参考文献

GenerationofMonoclonalAntibodiesagainstHighly ConservedAntigens HongzheZhou,YunboWang,WeiWang,JunyingJia,YuanLi,QiyuWang,YanfangWu,JieTang* CenterofInfectionandImmunity,NationalKeyLaboratoryofBiomacromolecules,InstituteofBiophysics,ChineseAcademyofSciences,Beijing,P.R.China Abstract Background: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generatinghigh-qualitymonoclonalantibodiesagainstagiventherapeutictargetisverycrucialforthesuccessofthedrug development.However,duetoimmunetolerance,someproteinsthatarehighlyconservedbetweenmiceandhumansare notveryimmunogenicinmice,makingitdifficulttogenerateantibodiesusingaconventionalapproach. Methodology/PrincipalFindings:Inthisreport,theimpairedimmunetoleranceofNZB/Wmicewasexploitedtogenerate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1)andonemouseself-antigen(TNF-alpha)asexamples,wedemonstrateherethatmultipleclonesofhighaffinity, highlyspecificantibodieswithdesiredbiologicalactivitiescanbegenerated,usingtheNZB/Wmouseastheimmunization hostandaTcell-specifictagfusedtoarecombinantantigentostimulatetheimmunesystem. Conclusions/Significance: We developed an efficient and universal method for generating surrogate or therapeutic antibodiesagainst‘‘difficultantigens’’tofacilitatethedevelopmentoftherapeuticantibodies. Citation:ZhouH,WangY,WangW,JiaJ,LiY,etal.(2009)GenerationofMonoclonalAntibodiesagainstHighlyConservedAntigens.PLoSONE4(6):e6087. doi:10.1371/journal.pone.0006087 Editor:DeryaUnutmaz,NewYorkUniversitySchoolofMedicine,UnitedStatesofAmerica ReceivedMarch11,2009;AcceptedMay28,2009;PublishedJune30,2009 Copyright: ? 2009 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported by the Nation