Researchmaterials/reagentsatthisstagetypicallyincludesurrogateantibodies,
Theprevioussectioninthisseriesis"AntibodyDrugDiscoveryOverview".Toreview,click here.
Assays:GenScripthasdevelopedseveralcell-basedADCC/CDCfunctionalassaystoprofiletheefficacyandpotencyofyourtherapeuticantibodiesusingproprietaryrecombinanteffectorcells.
Whataresomeoftheconsiderationsthatgointotargetselection?
AntibodySequencing:GenScript'sadvancedAntibodySequencingtechnologyoffersfastandprofessionalsequencingservicesforyourmonoclonalantibodies.
AntibodyEngineering:GenScriptscientists'extensiveexperienceinantibodyengineeringcanprovidesuperiorservicessuchasantibodyhumanization,affinitymaturationandmore.AntibodyProduction:Withsolidexpertiseinrecombinantantibody(rAb)productiontechniques,GenScriptprovidesacomprehensiverAbserviceportfoliothatdelivermicrogramtogramquantitiesofpurerAbforeachstageofyourAbdrugdiscoveryprogram.
TargetAssessment&Validation
1Shih,H.H.inDevelopmentofAntibody-BasedTherapeutics(edM.A;BornsteinTabrizi,G.G.;Klakamp,S.L.)Ch.2,9-32(Springer,2012).
definedashavinggatheredadequatescientificevidenceforthetarget'sdisease
transgenicanimalsandcelllines.Biologicalexperimentsalsoincludeknockout,
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GenScriptAntibodyDrugDiscoveryServices
criteriaandadditionalvalidationeffortsareoftenconducted.
transgenicanimalsorRNAitechniques.Majorityoftargetsmeetsomebutnotall
TargetIdentificationandValidation
Buthowisatargetselected?
YoucanalsoviewourRecombinantAntibodyServiceSelectionGuidetoidentifyservicesthatarethebestmatchforyourapplication.
Basedonpublisheddata:Literaturetarget,patentsetc.
intendedhumanproteinisobtainedasasurrogateAbtofacilitatetargetvalidation.
Deletionofthemouseorthologand/oroverexpressionofmouseproteinshouldmimichumanpathology1.
Ab-basedinterventionoftargetinananimalmimickinghumandiseaseshouldyieldthedesiredtherapeuticoutcome1.
邮箱:bioassay@genscript.com.cn;
TargetIdentification,
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TargetIdentification
studies,includingmousegenetics.Exampleslistedbelow:
电话:400-025-8686-5809
Targetaccessibility:ItshouldresideinphysiologicallocationaccessibletoAb.BraintargetsarenotoriouslydifficulttotreatusingAbtherapeuticsbecausetheblood-brainbarrierpreventstheirentryintobrain.SingledomainAbs/nanobodiescanhelpinsuchcasesowingtotheirsmallsize(~13kDa).
Expression:Shouldbeexpressedinpathologicaltissue.
"Omic"studies:Transcriptionalprofilingandproteomicsdatathatleadtothediscoveryofgenesandproteinswithaberrantexpressionpatternsindiseasestates.
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Concentration:ShouldbepresentatlevelthatisdetectableandcanbestoichiometricallyboundbyAbtherapeutic.Whathappensafteratargetisidentified?
Thefirststepafteratargethasbeenidentifiedistovalidateit.Validationissimply
AssessmentandValidation
PK/PDStudy:GenScriptoffersover120tumorandinflammationmodelsforevaluationofinvivoefficacy,PK/PD,biomarkerandbioanalysisstudies.GenScriptAnti-idiotypeAntibodyservicesarealsoapowerfultoolforantibodydrugPK/PDandimmunogenicitystudies.
AntibodyDiscovery:GenScript'sAntibodyEngineeringgroupcanbuildantibodylibrarywithupto1010individualclones,tospeedupyourantibodydiscoveryefforts.
References
Therapeuticstrategyisdefined:Forexample,acommonmolecularmechanismforanantibody-basedtherapeuticistheblockadeofaligand-receptorinteraction,forwhichtherearethreeconceivabletargetingstrategies:ananti-ligandantibody,ananti-receptorantibody,andareceptor-Fcfusionprotein1.
associationanditstherapeuticpotential.Thisisachievablethroughanimalmodel
TargetidentificationinAntibodyDrugDiscoveryistheprocessofidentifyingthemoleculartargetofanAntibody-usuallytargetcellsurfacemoleculessuchasreceptorsorantigensexpressedontumorcellsorotherhostcells.Stepsinvolveidentifyingdruggabletargets(definedasthelikelihoodofbeingabletomodulateatargetwithatherapeutic).Targetidentificationcanbeapproachedbydirectbiochemicalmethods,geneticinteractionsorcomputationalinference.Inmanycases,however,combinationsofapproachesmayberequiredtofullycharacterizeon-targetandoff-targeteffectsandtounderstandmechanismsofAb-bindingtothetargetantigen.
Typicallyamonoclonalantibody(mAb)recognizingthemouseorthologofthe
