推动CAR T细胞向前发展.ppt

DrivingCART?cellsforward推动CART细胞向前发展2016-11-24

1.TheCancer-ImmunityCycle

TheCancer-ImmunityCycle.ChenDS,etal.Immunity.2013Jul25;39(1):1-10.

ChenDS,etal.Immunity.2013Jul25;39(1):1-10.

StimulatoryandInhibitoryFactorsintheCancer-ImmunityCycle.ChenDS,etal.Immunity.2013Jul25;39(1):1-10.

KhalilDN,etal.NatRevClinOncol.2016May;13(5):273-90.

TherapiesthatMightAffecttheCancer-ImmunityCycleChenDS,etal.Immunity.2013Jul25;39(1):1-10.

Adoptivecelltransfer(ACT)1.TIL:Tumor-infiltratinglymphocyte2.CAR:Chimericantigenreceptor3.TCR:Tcellreceptor4.CytotoxicTlymphocyteRosenberg,S.?A.NatRevClinOncol.2011:8,577–585.

2.TIL:Tumor-infiltratinglymphocyte

ZhangL,etal.NEnglJMed.2003Jan16;348(3):203-13.GalonJ,etal.Science.2006Sep29;313(5795):1960-4.SurvivalAnalysesofPatientswithOvarianCarcinoma,AccordingtothePresenceorAbsenceofTILs.

TILtherapy.TranKQ,etal.JImmunother.2008Oct;31(8):742-51.

RosenbergSA,etal.ClinCancerRes.2011Jul1;17(13):4550-7.CombinationofRadiotherapyandImmunotherapy:ChangingtheGame.

3.CAR:Chimericantigenreceptor

Threesignalsarerequiredforantigen-specificTcellactivation.GutcherI,etal.JClinInvest.2007May;117(5):1119-27.

CAR-T-celldesign.

JacksonHJ,etal.NatRevClinOncol.2016Jun;13(6):370-83.CAR-T-celldesign.

CD19CAR-TCellTherapy.

ASH2015NEJM2013Apr18;368(16):1509-18.EmmainApril2012CD19CAR-TCellTherapy:ALongWayToGo.EmmatodayResponseRate:93%Relapse:1YearSurvival:79%1YearCR:55%SideEffect:CytokineStormBCellDepletion

ChenDS,etal.Immunity.2013Jul25;39(1):1-10.

多抗原负载促成熟皮下注射采集DC前体未成熟DCDC+淋巴细胞共培养静脉回输CTL诱导成熟DCCTL激活Flowchartofmultipleantigenstimulatingcellulartherapy(MASCT)

CherkasskyL,etal,JClinInvest.2016Aug1;126(8):3130-44.CotransductionofaPD-1DNRrescuesM28zCARTcells.

RT:radiother