美罗华在淋巴瘤治疗中的应用

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1、Lymphoma:ADecadeofRituximabandtheNextChapterWenruSong,MD,PhDPfizerGlobalResearch&Development-Oncology&BaylorInstituteforImmunologyResearchOutlineHistoricalperspective&reflectionsinRituximab’sdevelopmentImpactofRituximab-Lymphoma-Rheumatoidarthristis,lupus,andotherautoimmunediseases-Othersolidtu

2、morsNewemergingtherapiesinlymphomaMonoclonalAntibodiesfromHybridomaTechnologyAntigenCellsFuseintoaHybridomaCancerousPlasmaCellAntibody-producingPlasmaCellMonoclonalAntibodiesGeorgesKohlerandCesarMilstein(1975)inNature.Monoclonalantibodiesareartificiallyproducedagainstaspecificantigen.Production

3、ofmonoclonalantibodies(mAbs)withhybridomatechnique.Withthistechniqueagroupoflymphocytesproducingallthesameantibodyproteinisobtained.revolutionizingdiagnosticmedicine.Mabsagainstcancer,infections,andotherdiseases.HistoryofMonoclonalAntibody(Mab)TherapyMurineMab*Ibritomomab*tositumomabHumanized

4、*trastuzumab*bevacizumab*TheraCIMChimeric*Cetuximab*rituximab*131I-Ch-TNTHuman*panitumumabCH1CH3CH2VHCLVLCDR1975:FirstmurineMabfromhybridoma(KohlerandMilstein,Nature)1980’s-90’s:HumanizationofmurineMabs(chimericMab)1997:1stMabforcancerimmunotherapy:Rituximab1998:FullyhumanMab:-XenoMouse(Abgenix

5、),HuMab-mouse(Medarex)orPhagescFvlibrary1997-2007:11MabsapprovedforuseincancerbyUSFDAFDAApprovedMonoclonalAntibodiesYEARProductTargetIndication1986OrthocloneCD3TransplantRejection1994ReoProGPIIa/IIIbAngioplasty1997RituxanCD20BCellLymphoma1998ZenapaxIL2RTransplantRejection1998SimulectIL2RTranspl

6、antRejection1998RemicadeTNFCrohn’s,RA1998HerceptinHer2BreastCancer2000MylotargCD33AML2001CampathCD52CLL2002ZevalinCD20BCellLymphoma2003BexxarCD20BCellLymphoma2003RaptivaCD11aPsoriasis2004AvastinVEGFColonCancer20042004200620062007ErbituxTysabriLucentisVectibixSolirisEGFRa4b1integrinVEGF-AEGFRC5C

7、olonCancerMultiplesclerosisMaculardegenerationColonCancerPNHThe“Ups&Downs”ofMonoclonalAntibody(mAb)Development“Hey,thesearemagicbullets”“mAbsshouldbeeveninsoup”“Iheardtherearesomeproblems”“I’dapplythemonlytomyenemies”“mAbsworkinso