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1、腺相关病毒介导PSA基因转染DC的实验研究尤长宣罗荣城梁卫江南方医科大学南方医院肿瘤中心TheOncologyDepartmentofNanfangHospital,theSouthernMedicalUniversity,GuangzhouAdaptiveandInnateImmuneSystemsSkin&MucousMembranesrapidlyregeneratingsurfaces,peristalticmovement,mucociliaryescalator,vomiting,fl
2、owofurine/tears,coughingCellularandHumoralDefenseslysozyme,sebaceous/mucoussecretions,stomachacid,commensalorganisms,complementproteins,phagocytosis,naturalkillercellsInvasion&infectionBarriersInnateimmunityAdaptiveimmunityInflammationCellularandHumor
3、alDefensesAntibodies,cytokines,helperTcells,cytotoxicTcells（CTL）MK-0069-01Ag/MHCClassIIAg/MHCClassICD4ActivationCytokinesCD8TARGETLYSISActivation（CTL）Dendriticcell-MHCClassIrestricted-antigenspecificAntigenpresentationTumorantigenAntigenpositivetumorc
4、ellDendriticcellsexpressavarietyofcellsurfacemoleculeswhichplaykeyrolesintheirinteractionswithTcells.TheMHCmoleculespresentantigenicfragments(peptides)toTcellsinaformthatcanberecognizedinahighlyspecificfashionbytheappropriateTcellreceptor,whichisuniqu
5、eforeveryTcellandeveryantigen.Thecostimulatorymolecules(CD80andCD86)providea"second-signal"thatamplifiestheantigenrecognitionprocess.AccessorymoleculeslikeICAMsandLFAsenhancethephysicalinteractionbetweenTcellsandDCs.DendriticCellProperties前列腺癌细胞大量表达PS
6、APSA是前列腺细胞内的一种特异性蛋白；——前列腺癌标志物．选择PSA作为前列腺癌目标抗原．Loadingdendriticcellswith theantigen１．Protein/peptideloading２．GenedeliveryloadingDisadvantagesofProtein/peptideloadingT1/2ofproteins/peptidesisveryshort.Allarerapidlylost.2)Mostprotocolsforgeneratingcytoto
7、xicTlymphocytes（CTL）take3-5weeks.GenedeliveryloadingThegenecanproduceaconstantandlargeamountofprotein（ＰＳＡ）!!!!!VectorsforGenedeliveryRetroviruses(Retrov)(8kb,RNA,enveloped)Adenoviruses(Ad)(35kb,DNA,non-enveloped)Adeno-AssociatedVirus(AAV)(5kb,DNA,non-
8、enveloped)Retroviruses(Retrov)(8kb,RNA,enveloped)1)TransgeneinactivationbyDNAmethylation．2)Causescancer:proviralchromosomalintegrationactivatesproto-oncogene．3)Retrovirusvectorsareeasilydestroyed,easilyinactivated.Adenoviruses(Ad)(35kb,DNA,non
