Comparison of cell-based and non-cell-based assay platform[1]

《Comparison of cell-based and non-cell-based assay platform[1]》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、JIM-11973;NoofPages8JournalofImmunologicalMethodsxxx(2015)xxx–xxxContentslistsavailableatScienceDirectJournalofImmunologicalMethodsjournalhomepage:www.elsevier.com/locate/jimResearchpaperComparisonofcell-basedandnon-cell-basedassayplatformsforthedetectionofclinicallyrelev

2、antanti-drugneutralizingantibodiesforimmunogenicityassessmentoftherapeuticproteinsJennyHu⁎,IwonaWala,HongHan,JaniceNagatani,TroyBarger,FrancescaCivoli,ArunanKaliyaperumal,YaoZhuang,ShaliniGupta⁎ClinicalImmunology,AmgenInc.,ThousandOaks,CA91320,UnitedStatesarticleinfoabstr

3、actArticlehistory:Anti-drugneutralizingantibodies(NAbs)formedduetounwantedimmunogenicityofatherapeuticReceived3December2014proteinpointtowardsamatureimmuneresponse.NAbdetectionisimportantininterpretingtheReceivedinrevisedform11February2015therapeutic'sefficacyandsafetyinv

4、ivo.Invitrocell-basedNAbassaysprovideaphysiologicalsystemAccepted19February2015forNAbdetection,howeverarecomplexassays.Non-cell-basedcompetitiveligandbinding(CLB)AvailableonlinexxxxapproachesarealsoemployedforNAbdetection.Insteadofcells,CLBassaysusesolublereceptorandconju

5、gatedreagentsandareeasiertoperform,howeverhavereducedphysiologicalrelevance.TheKeywords:aimofthisstudywastocomparetheperformanceofCLBassaystoestablishedcell-basedassaystoCell-basedassaydeterminetheformer'sabilitytodetectclinicallyrelevantNAbstowardstherapeuticsthat(i)acte

6、dNon-cell-basedassayasanagonistor(ii)actedasantagonistsbybindingtoatargetreceptor.CompetitiveligandbindingassayWeperformedahead-to-headcomparisonoftheperformanceofcell-basedandCLBNAbassaysImmunogenicityforerythropoietin(EPO)andtwoanti-receptormonoclonalantibodies(AMG-Xand

7、AMG317).NeutralizingantibodiesNAbassayClinicallyrelevantNAb-positivesamplesidentifiedpreviouslybyacell-basedassaywereassessedinthecorrespondingCLBformat(s).Apanelof12engineeredfullyhumananti-EPOmonoclonalantibodies(MAbs)wastestedinbothEPONAbassayformats.Ourresultsshowedth

8、attheCLBformatwas(i)capableofdetectinghumananti-EPOMAbsofdifferingneutralizingcapabilitiesandaff