Chimeric Infectious Bursal Disease Virus-Like Particles as Potent Vaccines for Eradication of Established HPV-16 E7–Dependent Tumors.docVIP

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Chimeric Infectious Bursal Disease Virus-Like Particles as Potent Vaccines for Eradication of Established HPV-16 E7–Dependent Tumors.doc

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Chimeric Infectious Bursal Disease Virus-Like Particles as Potent Vaccines for Eradication of Established HPV-16 E7–Dependent Tumors

ChimericInfectiousBursalDiseaseVirus-LikeParticlesas PotentVaccinesforEradicationofEstablishedHPV-16 E7–DependentTumors JuanMartinCaballero1.,AnaGarzo′n2.¤a,LeticiaGonza′lez-Cintado3,WioletaKowalczyk4¤b, IgnacioJimenezTorres2¤c,GloriaCalderita2¤d,MargaritaRodriguez2¤e,Virg?′niaGondar2¤f ,Juan JoseBernal2¤g,CarlosArdav?′n3,DavidAndreu4,ThomasZu¨rcher2¤h,CayetanovonKobbe2*¤i 1Laboratory Animal Unit, Barcelona Biomedical Research Park, Barcelona, Spain, 2Cancer Vaccines Unit, R D Department, Chimera Pharma S.L.U., Madrid, Spain, 3DepartmentofImmunologyandOncology,CentroNacionaldeBiotecnolog?′a/CSIC,Madrid,Spain,4DepartmentofExperimentalandHealthSciences,PompeuFabra University,BarcelonaBiomedicalResearchPark,Barcelona,Spain Abstract Cervicalcanceriscausedbypersistenthigh-riskhumanpapillomavirus(HR-HPV)infectionandrepresentsthesecondmost frequentgynecologicalmalignancyintheworld.TheHPV-16typeaccountsforupto55%ofallcervicalcancers.TheHPV-16 oncoproteinsE6andE7arenecessaryforinductionandmaintenanceofmalignanttransformationandrepresenttumor- specificantigensfortargetedcytotoxicTlymphocyte–mediatedimmunotherapy.Therapeuticcancervaccineshavebecome a challenging area of oncology research in recent decades. Among current cancer immunotherapy strategies, virus-like particle(VLP)–basedvaccineshaveemergedasapotentandsafeapproach.Wegeneratedavaccine(VLP-E7)incorporating a long C-terminal fragment of HPV-16 E7 protein into the infectious bursal disease virus VLP and tested its therapeutic potentialinHLA-A2humanizedtransgenicmicegraftedwithTC1/A2tumorcells.Weperformedaseriesoftumorchallenge experimentsdemonstratingastrongimmuneresponseagainstalready-formedtumors(completeeradication).Remarkably, therapeuticefficacywasobtainedwithasingledosewithoutadjuvantandagainsttwoinjectionsoftumorcells,indicatinga potentandlong-lastingimmuneresponse. Citation:MartinCaballeroJ,Garzo′nA,Gonza′lez-CintadoL,KowalczykW,JimenezTorresI,etal.(2012)ChimericInfectiousBursalDiseaseVirus-LikeParticlesas Po