多发性骨髓瘤基因修饰瘤苗诱导体内抗肿瘤反应的实验研究论文

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1、多发性骨髓瘤基因修饰瘤苗诱导体内抗肿瘤反应的实验研究论文.freelyeloma(MM)remainsanincurablemalignancydespiteadvancesinchemotherapy.Myeloablativechemotherapyfolloatopoieticstemcelltransplantationhasincreasedtheincidenceofpleteremission，butalmostallpatientsachievingpleteremissionul

2、timatelyexperiencerelapse［1-3］.Becausethesechemotherapieshaveonlylimitedvalue，alternativestrategiesareneededtosolvetheseproblems.Immunotherapymayrepresentameansofmaintainingpleteremission.Basedonthefactthatmyelomacellscontainamultitudeoftumorantigenst

3、hatcaneffectivelystimulateantitumorTcells，severalinvestigatorshaverepor-tedimmunotherapeuticapproachesviainoculatingmye-ThisprojectentGrants’973’(No.2004CB518801andNo.2002CB713804)，ChineseHigh-TechProgram’863’(No.2003AA216050)andChineseNationalScience

4、Foundation(No.30400189).Correspondingauthor:edicine.lomacelllysates，yelomacellsorgeicallymodifiedmyelomacellvaccinestoaugmenttheimmunogenicityofmyelomacells.Numerousapplicationsofgenesencodingtumorsuppressiveproteins，cytokinesandcostimulatorymolecules

5、havebeenproposedincancer(includingMM)therapy［4-7］.Althoughtheresultsofmostpreclinicalinvestigationscarriedoutinvitroandinmousemodelsor-specificantigen，myelomacellsescapefromimmunesurveillancemainlybydoulatorymoleculesandinhibitinginductionandmaturatio

6、nofdendriticcells(DCs)［6，10-11］.Henceabinationofimmune-stimulatinggenesshouldbemoreefficientthananysinglegene.Inpreviousstudy，onstratedthatyelomacellvaccinationco-transferredanediatedbyrebinantadenovirusAd-p53/GM-CSF/B7-1inducesallologousandautologous

7、specificanti-tumorcytotoxicityinvitro［12］.Inthisstudyediatedimmunityisprotectiveagainstsubsequenttumorchallenge.NOD/SCIDmicearethemostimmunodeficientoftheSCIDvariants，andarethemostsupportivehostforhumanstemcells［13］.MostSCIDmousemyelomamodelshaveusedm

8、ouseorhumanMMcelllines.In2studies，freshBMCfromMMpatientsurvivedinconventionalSCIDmice，andinonegroupitanMMcelllinescolonizedinhumanfetalboneimplantedsubcutaneouslyinSCIDmice［14-16］.Hoicemyelomamodelscouldnotreflecttheinteractionbetanimmunesyste