Solid Tumor-Targeted Infiltrating Cytotoxic T Lymphocytes Retained by a Superantigen Fusion Protein 英文参考文献.docVIP

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Solid Tumor-Targeted Infiltrating Cytotoxic T Lymphocytes Retained by a Superantigen Fusion Protein 英文参考文献.doc

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Solid Tumor-Targeted Infiltrating Cytotoxic T Lymphocytes Retained by a Superantigen Fusion Protein 英文参考文献

SolidTumor-TargetedInfiltratingCytotoxicT LymphocytesRetainedbyaSuperantigenFusionProtein JialinSun*,LinaZhao,LijieTeng,FengLin,HongnaZhang,ZhengnanLi,QiangGao KeyLaboratory ofIndustrialMicrobiology, MinistryofEducation,CollegeofBiotechnology, TianjinUniversityofScienceandTechnology,Tianjin,People’sRepublicof China Abstract Successfulimmune-mediatedregressionofsolidtumorsisdifficultbecauseofthesmallnumberofcytotoxicTlymphocytes (CTLs)thatweretraffictothetumorsite.Here,thetargetingoftumor-specificinfiltratingCTLswasdependentonafusion protein consisting of human epidermal growth factor (EGF) and staphylococcal enterotoxin A (SEA) with the D227A mutation.EGF-SEAstronglyrestrainedthegrowthofmurinesolidsarcoma180(S180)tumors(controlversusEGF-SEA,mean + + tumor weight: 1.013 versus 0.197g, difference =0.816g). In mice treated with EGF-SEA, CD4 ,CD8 and SEA-reactive T lymphocyteswereenrichedaroundtheEGFRexpressingtumorcells.TheEGFreceptorswerepotentiallyphosphorylatedby EGF-SEAstimulationandthefusionproteinpromotedTcellstoreleasethetumoricidalcytokinesinterferon-c(IFN-c )and tumornecrosisfactor-a(TNF-a).IntratumoralCTLssecretedcytolyticpore-formingperforinsandgranzymeBproteinsnear thesurfaceofcarcinomas,causingthedeathofmanytumorcells.WeadditionallyshowthatlabeledEGF-SEAwasdirectly targetedtothetumortissueafterintravenous(i.v.)injection.Thefindingsdemonstratethatantibody-likeEGF-SEAplaysan importantroleinarrestingCTLsinthesolidtumorsiteandhastherapeuticpotentialasatumor-targetingagent. Citation: Sun J, Zhao L, Teng L, Lin F, Zhang H, et al. (2011) Solid Tumor-Targeted Infiltrating Cytotoxic T Lymphocytes Retained by a Superantigen Fusion Protein.PLoSONE6(2):e16642.doi:10.1371/journal.pone.0016642 Editor:XiaJin,UniversityofRochester,UnitedStatesofAmerica ReceivedNovember22,2010;AcceptedJanuary7,2011;PublishedFebruary2,2011 Copyright:?2011Sunetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distrib