therapeutic cell engineering治疗性细胞工程.pdfVIP

REViEw

:10.1038/nature22395

TherapeuticTcellengineering

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michelSadelain,isabelleRivièreStanleyRiddell

GicallyengineeredTcellsarepowerfulnewmedicines,offeringhopeforcurativeresponsesinpatientswithcancer.

Chimaericantigenreceptors(CARs)areaclassofsyntheticreceptorsthatreprogramlymphocytespecificityandfunction.

CARstargetin19havedemonstratedremarkablepotencyinBcellmalignancies.EngineeredTcellsareapplicablein

pripletomanycancers,pendingfurtherprogresstoidentifysuitabletarget,overcomeimmunosuppressive

tumourmicroenvironments,reducetoxicities,andpreventantigenescape.AdvancesintheselectionofoptimalTcells,

gicengineering,andcellmanufacturingarepoisedtobroadenT-cell-basedtherapiesandfosternewapplications

ininfectiousdiseasesandautoimmunity.

1

lymphocytesdevelopinthethymus,wheretheyacquiretheirRedirectingthespecificityofTcells

antigenreceptor,knownastheTcellreceptor(TCR)2.TcellsThemostnaturalapproachtotargetaTcelltoachosenantigenisto

Tareanessentialcomponentofadaptiveimmunity,contributingexpressthereinrearrangedTCRαandβchainsofdefinedpeci-

totumourrejectionandpathogenclearance.TheadoptivetransferofTficity,conformingtothephysiologicalTCR–CD3complex(Fig.1a).This

cellswasapivotalexperimentaltechniqueusedmorethanhalfacenturyprocedurewasusedintransgenicmicetodemonstratethattheTCR

agotoestablishthat