文献-comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human mal

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1、MedicalSciences:ChambersetalProc.NatlAcadScLUSA92(1995)1413Proc.Natl.Acad.Sci.USAVol.92,pp.1411-1415,February1995MedicalSciencesComparisonofgeneticallyengineeredherpessimplexvirusesforthetreatmentofbraintumorsinascidmousemodelofhumanmalignantglioma(oncolyticv

2、iruses/genetherapy/tumorcelltargeting)ReneeChambers*,G.YanceyGillespie*,LilianaSoroceanu*,SamitaAndreanskyI*，SUBHENDRACHATTERJEEt,JOANYCHOU*,BERNARDROIZMAN*,ANDRICHARDJ.WHITLEY§^Departmentsof*Neurosurgery,^PediatricsandMicrobiology,and^Pediatrics,Microbiology

3、andMedicine,UniversityofAlabamaatBirmingham,Birmingham,AL35284;and^TheMaijorieB.KovlerViralOncologyLaboratories,UniversityofChicago,Chicago,IL60637MedicalSciences:ChambersetalProc.NatlAcadScLUSA92(1995)1413MedicalSciences:ChambersetalProc.NatlAcadScLUSA92(199

4、5)1413ContributedbyBernardRoizman,October7,1994ABSTRACTGeneticallyengineeredvirusesandviralgenesinsertedintoretroviralvectorsareincreasinglybeingconsideredforexperimentaltherapyofbraintumors.Aprimarytargetofthesevirusesandvectorsishumangliomas,themostfrequen

5、tlyoccurringprimaryhumanbraintumor.Toinvestigatethepotentialofgeneticallyengineeredherpessimplexviruses(HSVs)inthetherapyofthesetumors,wecomparedtheattributesoftwoviruses,arecombinantfromwhichtheyi34.5genehadbeendeleted(R3616)andarecombinantinwhichtheyi34.5

6、genehadbeeninterruptedbyastopcodon(R4009).Previousstudieshaveshownthattheserecombinantswerecompletelydevoidoftheabilitytomultiplyinthecentralnervoussystemofrodents.Topursuethesestudies，wedevelopedascidmousegliomamodel.Tumorcellresponse(survival)for103,104,a

7、nd105implantedMT539MGgliomacellswas38，23，and15days,respectively.Theresultswereasfollows:(i)bothR3616andR4009replicateandcausecytol-ysisindiversegliomacelllinesofmurineandhumanorigininvitro,and(ii)inWinn-typeassays105MT539MGcellscoinoculatedwithR3616orR4009asc

8、omparedtosalinesignificantlyprolongedsurvivalinadose-dependentfashion.Micethatreceivedonlytumorcellsorthewild-typeparentstrainoftherecombinants,HSV-l(F),diedwithin15days.Survivalwasgreate