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1、ARTICLEReceived15Jul2016
2、Accepted22Sep2016
3、Published31Oct2016DOI:10.1038/ncomms13354OPENStructuralbasisofcheckpointblockadebymonoclonalantibodiesincancerimmunotherapyJuYeonLee1,*,HyunTaeLee1,*,WooriShin1,*,JongseokChae1,JaemoChoi1,SungHyunKim1,HeejinLim1,TaeWonHeo1,KyeongYoungPar
4、k1,YeonJiLee1,SeongEonRyu2,JiYoungSon1,JeeUnLee1&Yong-SeokHeo1Cancercellsexpresstumour-specificantigensderivedviageneticandepigeneticalterations,whichmaybetargetedbyT-cell-mediatedimmuneresponses.However,cancercellscanavoidimmunesurveillancebysuppressingimmunitythroughactivationof
5、specificinhibitorysignallingpathways,referredtoasimmunecheckpoints.Inrecentyears,theblockadeofcheckpointmoleculessuchasPD-1,PD-L1andCTLA-4,withmonoclonalantibodieshasenabledthedevelopmentofbreakthroughtherapiesinoncology,andfourtherapeuticantibodiestargetingthesecheckpointmolecule
6、shavebeenapprovedbytheFDAforthetreatmentofseveraltypesofcancer.Here,wereportthecrystalstructuresofcheckpointmoleculesincomplexwiththeFabfragmentsoftherapeuticantibodies,includingPD-1/pembrolizumab,PD-1/nivolumab,PD-L1/BMS-936559andCTLA-4/tremelimumab.Thesecomplexstructureselucida
7、tethepreciseepitopesoftheantibodiesandthemolecularmechanismsunderlyingcheckpointblockade,providingusefulinformationfortheimprove-mentofmonoclonalantibodiescapableofattenuatingcheckpointsignallingforthetreatmentofcancer.1DepartmentofChemistry,KonkukUniversity,120Neungdong-ro,Gwang
8、jin-gu,Seoul05029,RepublicofKorea.2DepartmentofBioEngineering,HanyangUniversity,222Wangsimni-ro,Seongdong-gu,Seoul04763,RepublicofKorea.*Theseauthorscontributedequallytothiswork.CorrespondenceandrequestsformaterialsshouldbeaddressedtoY.-S.H.(email:ysheo@konkuk.ac.kr).NATURECOMMUN
9、ICATIONS
10、7:13354
11、DOI:10.1038/ncomms13354
12、www.nature.com/naturecommunications1ARTICLENATURECOMMUNICATIONS
13、DOI:10.1038/ncomms13354stheimmunesystemplaysanimportantrolein(pembrolizumabandnivolumab),andPD-L1(atezolizumab)forcontrollingcancer,utilizingtheimmunesystemtothetreatmentofmel
14、anoma,non-small-celllungcancer,renalcell
