肝癌中基因修飾的細胞免疫治療的實驗研究.pdf

1、復旦大學博士學位論文肝癌中基因修飾的細胞免疫治療的實驗研究姓名：鄭寧申請學位級別：博士專業(yè)：腫瘤學指導教師：葉勝龍2002.4.30英文摘要GeneticallyModifiedCellularImmunotherapyforLiverCancerAbstractSincethecellularimmuneresponsesplaystheleadingrolefortherejectionofcancersinhumanbodies，

2、cellularimmunotherapy，whichusesimmunocytesasthestaplevectors，hasbecomeprincipletreatmentforcancersRecently，toenhancethecurativeeffectofcellularimmunotherapyforcancerbygeneticallymodifyingtheimmunocytesisoneofthehighlight

3、sofcancerresearchInordertostudythesynergisticantitumoractivityofdifferentmodalitiesofcellularimmunotherapyforhepatocellularcarcinoma(Hcc)，weobservedthecombinationroleofgeneticallymodifieddendriticcells(DC)andadherentLAK(

4、ALAIC)cellsforlivercancersTheresultsshowedthat：(1)SufficientDCandALAKcellswithhighbiologicaleffectwereobtainedfromtheperipheralbloodmononuclearcells(PBMC)oflivercancerpatientsWithcryopreservationandphenylacetate，theimmun

5、oactivitiesofA—LAKcellsfrompatientswithHCCcouldbeclearlyincreased(2)WeclonedthefulllengthcDNAofhumanFit3ligand(FL)geneandhumanIL18genefromPBMC，andconstructedthemintotherecombinantadenovirusvectorsseparatelyWealsoobtained

6、an州isoformofFLgenewithaspecific54bpdefectioninexon5(3)CombinedadministrationofDCandA_LAKcellswithexogenousFLandIL18genesmodificationcouldsynergisticallyenhancetheantiHCCeffectboth／nvitroandinamouselivercancermodelTheresu

7、ltsindicatedthatgeneticallymodificationofimmunocytescouldsignificantlyimprovetheirbioactivitiesFurthermore，combinedusageofDCandA—LAKcellscansimultaneouslysuppressthemultiplestepsofimmunoescapemechanismoftumorsinhumanbodi

8、es，andplaythecomprehensiveantitumorrolesincludingboththespecificactiveimmunotherapyinducedbyDCandthenonspecificpassive(oradoptive)immunotherapyinducedbyALAKcells，thustheantitumoreffectofHCCisstrengthenedKeywords：LiverCan