Monoclonal AntibodiesMonoclonal AntibodiesRaymond LiuRaymond LiuBiochemistry 118QBiochemistry 118QSpring 2004Spring 2004OverviewOverviewMonoclonal AntibodiesMonoclonal AntibodiesApplicationsApplicationsGenomicsGenomicsDrug DevelopmentDrug DevelopmentSmart BombsSmart BombsSpecificitySpecificityTargetingTargetingVarietyVarietyAntibodies and the Immune SystemAntibodies and the Immune SystemAntibodies and the Immune SystemAntibodies and the Immune SystemB-cellsB-cellsSplicingSplicingLimitlessLimitlessAntibodies and the Immune SystemAntibodies and the Immune SystemMonoclonal AntibodiesMonoclonal AntibodiesSingle SpecificitySingle SpecificityUnlimited ProductionUnlimited ProductionMonoclonal AntibodiesMonoclonal AntibodiesMonoclonal AntibodiesMonoclonal Antibodies1975- K1975- Kööhler andhler andMilsteinMilsteinImmunized miceImmunized miceFused B cells withFused B cells withmyeloma cellsmyeloma cellsHybridomasHybridomasNobel PrizeNobel PrizeApplicationsApplications Grouping blood types and identifying viruses Labeling in tests for pregnancy, cancers, bloodclots, and heart disease. Purification of proteins and drugs Counteract transplant rejectionApplicationsApplicationsFluorescence ImagingFluorescence ImagingCarrier molecule Carrier molecule –– radioactive cargo, cytotoxins, etc. radioactive cargo, cytotoxins, etc.Binds receptorsBinds receptorsApplicationsApplicationsRituxan Rituxan –– CD20 on B CD20 on Bcells (Ron Levy)cells (Ron Levy)Herceptin Herceptin –– HER2, EGF HER2, EGFreceptorreceptorVitaxin Vitaxin –– vascular vascularintegrin, antiangiogenesisintegrin, antiangiogenesisProblemsProblemsMouse antibodies foreignMouse antibodies foreignProduction of human anti-mouse antibodiesProduction of human anti-mouse antibodies(HAMA)(HAMA)Rapid inactivationRapid inactivationSolutionsSolutionsChimeric antibodies Chimeric antibodies –– human-mouse hybrid human-mouse hybridantibodies with mouse CDR fused with humanantibodies with mouse CDR fused with humanconstant regionsconstant regionsSplicing mouse CDR into human antibody geneSplicing mouse CDR into human antibody generegionsregionsTransgenic miceTransgenic miceGenomicsGenomicsGenomicsGenomicsGenomic databasesGenomic databasesMicroarraysMicroarraysAdditional ScreeningsAdditional ScreeningsAntibody productionAntibody productionGenomicsGenomicsIdentify surface receptorsIdentify surface receptorsassociated with majorassociated with majorcancerscancersSearch genome databasesSearch genome databasesfor genes regulatingfor genes regulatingreceptorsreceptorsGenomicsGenomicsCompare gene sequencesCompare gene sequencesto that of living cancerto that of living cancercellscellsUse microarrays to findUse microarrays to findgenes active in cancergenes active in cancerbut not in normal cellsbut not in normal cellsIdentify target receptorIdentify target receptorproteinsproteinsGenomicsGenomicsInject mouse withInject mouse withproteinproteinExtract antibodiesExtract antibodiesTest against cancer cellsTest against cancer cellsContinue drugContinue drugdevelopment processdevelopment processOutlookOutlook Transplant rejection, Cancer, Autoimmunediseases, infectious diseases Creation of libraries with antibodies againstdifferent antigensMonoclonal AntibodiesMonoclonal
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