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1、REVIEWSBuildingbettermonoclonalantibody-basedtherapeuticsGeorgeJ. WeinerAbstract
2、For20 years,monoclonalantibodies(mAbs)havebeenastandardcomponentofcancertherapy,butthereisstillmuchroomforimprovement.EffortscontinuetobuildbettercancertherapeuticsbasedonmAbs.Antican
3、cermAbsfunctionthroughvariousmechanisms,includingdirectlytargetingthemalignantcells,modifyingthehostresponse,deliveringcytotoxicmoietiesandretargetingcellularimmunitytowardsthemalignantcells.CharacteristicsofmAbsthataffecttheirefficacyincludeantigenspecificity,ove
4、rallstructure,affinityforthetargetantigenandhowamAbcomponentisincorporatedintoaconstructthatcantriggertargetcelldeath.ThisReviewdiscussesthevariousapproachestousingmAb-basedtherapeuticstotreatcancerandthestrategiesusedtotakeadvantageoftheuniquepotentialofeachappro
5、ach,andprovidesexamplesofcurrentmAb-basedtreatments.Morethantwocenturieshavepassedsincewebegantotheirclinicalutility.Theseproblemsincludedthedevelop-Clusterofdifferentiationnumbersunderstandtheremarkablecharacteristicsandpotentialmentofanimmuneresponseagainsttheth
6、erapeuticofantibodies1.Indeed,polyclonalantiserahavebeenusedmAbitself,therapidclearanceofthemAbandthesub-Numbersassignedtocellsurfacemoleculesonthebasisinthetreatmentofcertaininfectiousdiseasesfordecades2.optimalabilityofthemurinemAbtointeractwiththeofimmunophenot
7、yping.TheySoonafterthefirstdescriptionofmonoclonalanti-humanimmunesysteminamannerthatledtoimmuneareoftenusedtoidentifybodies(mAbs)in1975(REF. 3)(adiscoverythatledtodestructionofthe cancer.differentmonoclonalaNobelPrize10 yearslater4),mAbswererecognizedFortunately,
8、persistentinvestigatorscontinuedtoantibodiesthatbindtothesameantigen.asuniquebiologicaltoolsandquicklybecameinvalu-explorehowmAbscouldbeusedincancertreatment.ableinpathologicaldiagnosisandbasiclaboratoryTheyevaluatedvariousstrategies,includingusinginvestigation.Th
9、eirabilitytobindtospecificantigenicimmunoglobulinG(IgG)totargetcancerdirectly,alterepitopesallowedfortherapidassessmentofthemolecu-thehostresponsetocanc
