Bladder Cancer Immunotherapy BCG and Beyond英文文献资料.docVIP

HindawiPublishingCorporation AdvancesinUrology Volume2012,ArticleID181987,13pages doi:10.1155/2012/181987 ReviewArticle BladderCancerImmunotherapy:BCGandBeyond EricJ.Askeland,MarkR.Newton,MichaelA.O’Donnell,andYiLuo DepartmentofUrology,UniversityofIowa,375NewtonRoad,3204MERF,IowaCity,IA52242,USA CorrespondenceshouldbeaddressedtoYiLuo,yi-luo@ Received16March2012;Accepted11May2012 AcademicEditor:TrinityJ.Bivalacqua Copyright?2012EricJ.Askelandetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. MycobacteriumbovisbacillusCalmette-Gu′erin(BCG)hasbecomethepredominantconservativetreatmentfornonmuscleinvasive bladder cancer. Its mechanism of action continues to be de?ned but has been shown to involve a T helper type 1 (Th1) immunomodulatoryresponse.WhileBCGtreatmentisthecurrentstandardofcare,asigni?cantproportionofpatientsfailsordo nottoleratetreatment.Therefore,manye?ortshavebeenmadetoidentifyotherintravesicalandimmunomodulatingtherapeutics tousealoneorinconjunctionwithBCG.Thispaperreviewstheprogressofbasicscienceandclinicalexperiencewithseveral immunotherapeuticagentsincludingIFN-α,IL-2,IL-12,andIL-10. 1.Introduction patientswillbeBCGfailures[5–7].Ofthecompleterespon- ders,upto50%willhavearecurrence[8].Furthermore,side e?ectsrangefromcystitisandirritativevoidingsymptomsto muchmoreuncommonlife-threateningBCGsepsis.Upto 20%ofpatientsareBCGintolerantduetothesesidee?ects [9]. Understanding of BCG, both its mechanisms (which remainincompletelycharacterized)anditsobviouslimita- tions, is critical to improving the e?cacy of therapy. The initial step after BCG instillation is binding of BCG to ?bronectin expressed on the urothelium, after which the mycobacterium is internalized by both normal and malig- nantcells,resultinginurothelialactivationandsubsequent in?ammatoryresponsesinthebladder[10].BCGantigens canbepresentedatthec