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1、晚期肺癌免疫治疗浙江大学附属第一医院肿瘤内科Theimmunesystem:最佳武器w一多样¥精确♦持久an“ideal"anti-cancerweaponDiverseattackTcells,antibodies,naturalkillers,etc....Pre£!sejarget^Candistinguishminute；chemicalalterations力RecallaAftereffectivepriming,iimmunitycanlastforalifetime肿瘤免疫治疗方式repiiaevaccine二DCvaccine.Gene
2、ticvaccine-一®%7ActiveimmunotherapyAdoptivecelltransfer1immunotherapyTcellcloningCD40J] X40_____
3、w=—PD>•••TCRorCARgeneticengineering癌症抵御免疫调节抑制检查点Thewallsofcancer'sdefenseagainstimmuneattackRegulatoryimmunecellsSuppressivecytokinesImmune“checkpoints”CTLA-4和PD-1/L1检查点阻断Primingphase(
4、lymphnode)Effectorphase(peripheraltissue)RibasA.NEnglJMed.2012;366:2517-2519.Breakthroughorevolution??CTLA-4CloningofCTLA-4geneTDemonstrationoforgan-specificautaimmunityinPD-1KOmkePD-L1expressionintrurinetumorsconfersimmuneresistanceshighPD-LIexpressioninhumantumorsFIrstd&monstrat
5、banofcltnka!activityofanti-PD-l^Cloningo^lPD-1PD-L1/PD-L2IdentifiedasPD-1ligandspnti-PO-ljPredictedFDAapprovalofantB-PD-1Anti-POl&anthPOLlinducedurabletumorresponsesinmelanoma,,kidney&lungcancerPardoli,NatureImmunoi2012CLINICALPRACTICE-2015ROS1ISTITUTUN^ZIOMALEperloStudioELi.CURAD
6、EITur.lORIIzjEIITEDAT：AnnualMeeting肿瘤药物的发展策略二线治疗新联合化疗一线治疗新单药后线治疗辅助/新辅助多西他赛疗效恒定•肺癌的高频率体细胞突变可能导致其免疫原性增加2•靶向于PD-L1/PD-1通路的治疗将会改变肺癌的治疗1经允许复制干MacHllanPublishersLtdLawrenceMS,etal.Nature:2013;499(7457)214-218.copyright20132chenDSetal.CCR2012Alexander/etal.ASCO2015Abstract8010抗PD-1检查点抑制剂
7、临床研发（实体瘤）AntibodyMoleculeDevelopmentStageApproved(US):advancedmelanomaafterpreviousNivolumabFullyhumanIgG4therapy,advancedsquamousNSCLCafterCTPhaseIIImultipletumors(NSCLC,melanoma,RCCfHNSCCfGBM,gastric)Approved(US):advancedmelanomaafterpreviousPembrolizumabHumanizedIgG4therapyPhas
8、eIIImultipletumors(HNSCC,NSCLCfmelanoma,bladder,gastric/GE)PidilizumabHumanizedIgGlPhaseIImultipletumors(pancreatic,CRCfRCC,prostate,CNS)AMP-224Fc-PD-L2fusionproteinPhaseI抗PD・L1检查点抑制剂临床研发（实体痛）AntibodyMoleculeDevelopmentStageMEDI4736(durvalumab)EngineeredhumanIgGlPhaseIIImultipletu
9、mors(NSCLCfHNSCC)MPDL3280A(atezol
