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.
