EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL 英文参考文献.docVIP

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EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL 英文参考文献.doc

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EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL 英文参考文献

EBV-gp350ConfersB-CellTropismtoTailoredExosomes andIsaNeo-AntigeninNormalandMalignantBCells— ANewOptionfortheTreatmentofB-CLL RomanaRuiss1,SimonJochum1,RalphMocikat2,WolfgangHammerschmidt1,ReinhardZeidler3* 1DepartmentofGeneVectors,Helmholtz-Zentrum,Munich,Germany,2Institutfu¨rMolekulareImmunologie,Helmholtz-Zentrum,Munich,Germany,3Departmentof Otorhinolaryngology,Ludwig-Maximilians-Universita¨t, Munich,Germany Abstract gp350,themajorenvelopeproteinofEpstein-Barr-Virus,confersB-celltropismtothevirusbyinteractingwiththeBlineage markerCD21.Hereweutilizegp350togeneratetailoredexosomeswithanidenticaltropism.Theseexosomescanbeused forthetargetedco-transferoffunctionalproteinstonormalandmalignanthumanBcells.Wedemonstrateheretheco- transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfmentofgp350+exosomesbyB-CLLcellsandpresentationofgp350-derivedpeptidesalsore-stimulatedEBV-specific TcellsandredirectedthestrongantiviralcellularimmuneresponseinpatientstoleukemicBcells.Inessence,weshowthat gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailoredexosomesandasaneo-antigeninmalignantBcellsprovidesanovelattractivestrategyforimmunotherapyofB- CLLandotherB-cellmalignancies. Citation:RuissR,JochumS,MocikatR,HammerschmidtW,ZeidlerR(2011)EBV-gp350ConfersB-CellTropismtoTailoredExosomesandIsaNeo-Antigenin NormalandMalignantBCells—ANewOptionfortheTreatmentofB-CLL.PLoSONE6(10):e25294.doi:10.1371/journal.pone.0025294 Editor:GabrieleMulthoff,TechnischeUniversitaetMuenchen,Germany ReceivedJuly27,2011;AcceptedAugust31,2011;PublishedOctober10,2011 Copyright: ? 2011 Ruiss et al. This is an open-access article distributed under the te