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Antibody-Based Therapies in Multiple Myeloma英文文献资料.doc

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Antibody-Based Therapies in Multiple Myeloma英文文献资料

HindawiPublishingCorporation BoneMarrowResearch Volume2011,ArticleID924058,14pages doi:10.1155/2011/924058 ReviewArticle Antibody-BasedTherapiesinMultipleMyeloma Yu-TzuTaiandKennethC.Anderson DepartmentofMedicalOncology,JeromeLipperMultipleMyelomaCenter,Dana-FarberCancerInstitute,HarvardMedicalSchool, 44BinneyStreet,Boston,MA02115,USA CorrespondenceshouldbeaddressedtoYu-TzuTai,yu-tzutai@ Received18October2010;Accepted4January2011 AcademicEditor:IgnazioMajolino Copyright?2011Y.-T.TaiandK.C.Anderson. This is an open access article distributed under the Creative Commons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. Theunmetneedforimprovedmultiplemyeloma(MM)therapyhasstimulatedclinicaldevelopmentofmonoclonalantibodies (mAbs)targetingeitherMMcellsorcellsofthebonemarrow(BM)microenvironment.Incontrasttosmall-moleculeinhibitors, therapeuticmAbspresentthepotentialtospeci?callytargettumorcellsanddirectlyinduceanimmuneresponsetolysetumor cells.Uniqueimmune-e?ectormechanismsareonlytriggeredbytherapeuticmAbsbutnotbysmallmoleculetargetingagents. AlthoughtherapeuticmurinemAbsorchimericmAbscancauseimmunogenicity,theadvancementofgeneticrecombinationfor humanizingrodentmAbshasallowedlarge-scaleproductionanddesignationofmAbswithbettera?nities,e?cientselection, decreasingimmunogenicity,andimprovede?ectorfunctions.Theseadvancementsofantibodyengineeringtechnologieshave largelyovercomethecriticalobstacleofantibodyimmunogenicityandenabledthedevelopmentandsubsequentFoodandDrug Administration(FDA)approvaloftherapeuticAbsforcancerandotherdiseases. 1.Introduction interleukin-6 (IL-6), vascular endothelial growth factor (VEGF),ReceptorActivatorofNFκBligand(RANKL)(also known as osteoprotegerin ligand (OPGL)), and Dickkopf homolog 1 (DKK1) are among those under clinical evalu- ation.Speci?cally,targetingbone-MMcellinteractions via bonebiologymodulatingfactorssuchasDKK1andRANKL islikelytotriggeranti-MMe?ectsbut