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《Nature Reviews Drug Discovery 2012.04.pdf》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、REVIEWSFcreceptor-targetedtherapiesforthetreatmentofinflammation,cancerandbeyondP.MarkHogarth1,2,3andGeoffreyA.Pietersz2,3,4Abstract
2、ThedirectorindirecttargetingofantibodyFcreceptors(FcRs)presentsuniqueopportunitiesandinterestingchallengesforthetreatmentofinflammato
3、rydiseases,cancerandinfection.BiologicalresponsesinducedviatheFcportionsofantibodiesarepowerful,complexandunusual,andcomprisebothactivatingandinhibitoryeffects.Thesepropertiescanbeexploitedintheengineeringoftherapeuticmonoclonalantibodiestoimprovetheiractivityin viv
4、o.FcRshavealsoemergedaskeyparticipantsinthepathogenesisofseveralimportantautoimmunediseases,includingsystemiclupuserythematosusandrheumatoidarthritis.TherapeuticapproachesbasedonantagonizingFcRfunctionwithsmallmoleculesorbiologicaldrugssuchasmonoclonalantibodiesandr
5、ecombinantsolubleFcRectodomainshavegainedmomentum.ThisReviewaddressesvariousstrategiestomanipulateFcRfunctiontoovercomeimmunecomplex-mediatedinflammatorydiseases,andconsidersapproachestoimproveantibody-basedanticancertherapies.Antibodiesorimmunoglobulinsarethesolubl
6、emedia-mediatedbyasingleinhibitoryreceptor—FcγRIIb—Antibody-dependentcell-mediatedcytotoxicitytorsofimmunologicalresistancetoinvadingpathogens.thatexistsinseveralforms,mostlyasvariantsofthecyto-(ADCC).AmechanismofkillingMillionsofyearsofevolutionhavefine-tunedtheact
7、ivityplasmictail.Recently,however,ithasbecomeapparentthatantibody-coatedcellsbyoftheseveryspecificandeffectivemediatorsofhostpro-someoftheactivatingFcRsexhibitaparadoxicaldualismeffectorcells(forexample,tection.Mostimportantly,sophisticatedeffectorsystemsoffunctiona
8、ndmayalsodeliverinhibitorysignals4–7.naturalkillercells,neutrophilshaveco-evolvedwithantibodiesandareresponsibleforInthecontextofdrugdiscovery,FcRtargetingcanoreosinophils).theirnormallyprotectivebiologicaleffects.Principalbeconsideredfromthreeunrelatedperspectives.
9、First,1Inflammation,Canceramongtheseeffectorsystemsarethoseinducedviatheinautoimmunityorotherantibody-dependenthyper-andInfectionLaborator
