Oncolytic Adenoviruses Armed with Thymidine Kinase Can Be Traced by PET Imaging and Show Potent Antitumoural Effects by Ganciclovir Dosing 英文参考文献.docVIP

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Oncolytic Adenoviruses Armed with Thymidine Kinase Can Be Traced by PET Imaging and Show Potent Antitumoural Effects by Ganciclovir Dosing 英文参考文献.doc

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Oncolytic Adenoviruses Armed with Thymidine Kinase Can Be Traced by PET Imaging and Show Potent Antitumoural Effects by Ganciclovir Dosing 英文参考文献

OncolyticAdenovirusesArmedwithThymidineKinase CanBeTracedbyPETImagingandShowPotent AntitumouralEffectsbyGanciclovirDosing DanielAbate-Daga1,2,NuriaAndreu2,3,JuanCamacho-Sa′nchez4,RamonAlemany4,Rau′lHerance5 ,Olga Milla′n5¤,CristinaFillat1,2,3* 1Institut D’Investigacions Biome`diques August Pi i Sunyer-IDIBAPS, Barcelona, Spain, 2Centre de Regulacio′ Geno`mica (CRG), UPF, Barcelona, Spain, 3Centro de Investigacio′n Biome′dica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain, 4Gene and Viral Therapy Group, IDIBELL-Catalan Institute of Oncology (ICO), L’HospitaletdeLlobregat,Barcelona,Spain,5Institutd’AltaTecnologia,PRBBFundacio′ Privada,Barcelona,Spain Abstract Replication-competentadenoviruses armedwiththymidinekinase(TK)combinetheconceptsofvirotherapyandsuicide gene therapy. Moreover TK-activity can be detected by noninvasive positron emission-computed tomography (PET) imaging, what could potentially facilitate virus monitoring in vivo. Here, we report the generation of a novel oncolytic adenovirusthatincorporatestheTat8-TKgeneunderthecontroloftheMajorLatePromoterinahighlyselectivebackbone thusprovidingselectivitybytargetingtheretinoblastomapathway.TheselectiveoncolyticTKvirus,termedICOVIR5-TK-L, showed reduced potency compared to a non-selective counterpart. However the combination of ICOVIR5-TK-L with ganciclovir (GCV) induced a potent antitumoural effect similar to that of wild type adenovirus in a preclinical model of pancreaticcancer.AlthoughthetreatmentwithGCVprovokedareductionintheviralyield,bothinvitroandinvivo,atwo- cycletreatmentofvirusandGCVresultedinanenhancedantitumoralresponsethatcorrelatedwithhighTK-activity,based onmicroPETmeasurements.Thus,TK-expressingoncolyticadenovirusescanbetracedbyPETimagingprovidingrealtime informationontheactivityofthevirusanditsantitumoralpotencycanbeoptimizedbyGCVdosing. Citation:Abate-DagaD,AndreuN,Camacho-Sa′nchezJ,AlemanyR,HeranceR,etal.(2011)OncolyticAdenovirusesArmedwithThymidineKinaseCanBeTraced byPETIm