An Efficient Strategy to Induce and Maintain In Vitro Human T Cells Specific for Autologous Non-Small Cell Lung Carcinoma 英文参考文献.docVIP

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An Efficient Strategy to Induce and Maintain In Vitro Human T Cells Specific for Autologous Non-Small Cell Lung Carcinoma 英文参考文献.doc

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An Efficient Strategy to Induce and Maintain In Vitro Human T Cells Specific for Autologous Non-Small Cell Lung Carcinoma 英文参考文献

AnEfficientStrategytoInduceandMaintainInVitro HumanTCellsSpecificforAutologousNon-SmallCell LungCarcinoma GlendaCanderan1¤a,PaolaGruarin1¤b,DanielaMontagna2,RaffaellaFontana3,GiulioMelloni4 ,Catia Traversari5,PaoloDellabona1*,GiuliaCasorati1* 1Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy, 2Laboratory of Immunology,DepartmentofPediatrics,UniversityofPavia,Pavia,Italy,3CancerGeneTherapyUnit,DivisionofMolecularOncology,SanRaffaeleScientificInstitute,Milan, Italy,4DepartmentofThoracicSurgery,SanRaffaeleScientificInstitute,Milan,Italy,5MolMedS.P.A.,Milan,Italy Abstract Background:TheefficientexpansioninvitroofcytolyticCD8+Tcells(CTLs)specificforautologoustumorsiscrucialbothfor basicandtranslationalaspectsoftumorimmunology.WeinvestigatedstrategiestogenerateCTLsspecificforautologous Non-SmallCellLungCarcinoma(NSCLC),themostfrequenttumorinmankind,usingcirculatinglymphocytes. PrincipalFindings:ClassicMixedLymphocyteTumorCultureswithNSCLCcellsconsistentlyfailedtoinducetumor-specific CTLs.Cross-presentationinvitroofirradiatedNSCLCcellsbyautologousdendriticcells,bycontrast,inducedspecificCTL lines from which we obtained a high number of tumor-specific T cell clones (TCCs). The TCCs displayed a limited TCR diversity, suggesting an origin from few tumor-specific T cell precursors, while their TCR molecular fingerprints were detectedinthepatient’stumorinfiltratinglymphocytes,implyingaroleinthespontaneousanti-tumorresponse.Grafting NSCLC-specificTCRintoprimaryallogeneicTcellsbylentiviralvectorsexpressinghumanV-mouseCchimericTCRa/bchains + + overcamethegrowthlimitsoftheseTCCs.Theresulting,rapidlyexpandingCD4 andCD8 Tcelllinesstablyexpressedthe graftedchimericTCRandspecificallyrecognizedtheoriginalNSCLC. Conclusions:ThisstudydefinesastrategytoefficientlyinduceandpropagateinvitroTcellsspecificforNSCLCstartingfrom autologousperipheralbloodlymphocytes. Citation:CanderanG,GruarinP,Mon