Intratumoral Expression of MIP-1β Induces Antitumor Responses in a Pre-Established Tumor Model through Chemoattracting T Cells and NK Cells

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摘要 Directintratumoralintroductionoftherapeuticorregulatorygenesisadevelopingtechnologywithpotentialapplicationforcancergenetherapy.Macrophageinflammatoryprotein-1beta(MIP-1β)isachemokinewhichcanchemoattractimmunecellssuchasTcells.Inthepresentstudy,murinecolorectaladenocarcinomaCT26cellsweretransfectedwitharecombinantadenovirus(AdhMIP-1β)carryingthehumanMIP-1βgene.24hpost-transfection,hMIP-1βlevelsreachedapproximately980pg/mlinsupernatantsof106hMIP-1β-transfectedCT26cells.Moreover,thesupernatantsexhibitedchemotacticactivityforCD8+Tcells,CD4+Tcells,NKcellsandimmatureDCs.IntratumoralinjectionofAdhMIP-1βsignificantlyinhibitedtumorgrowthandprolongedthesurvivaltimeoftumor-bearingmice.IntratumoralhMIP-1βgenetransferalsoinducedpowerfultumor-specificCTLresponsesinvivo.ThetherapeuticeffectsofhMIP-1βgenetherapyweregreatlyreducedfollowinginvivodepletionofbothCD4+andCD8+Tcells,butwereunaffectedbydepletionofsingleTcellsubsets.ImmunecelldepletionexperimentsalsorevealedthatNKcellsplayedanimportantroleinhMIP-1β-inducedantitumorresponses.TheseresultssuggestthatintratumoralexpressionofhMIP-1βhasthepotentialeffecttoinducehostantitumorimmunityandmayprovetobeausefulformofcancergenetherapy.
机构地区 不详
出版日期 2004年03月13日(中国期刊网平台首次上网日期,不代表论文的发表时间)
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