Chimeric antigen receptor-engineered T cells for the treatment of metastatic prostate cancer

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1、BioDrugsDOI10.1007/s40259-015-0122-9LEADINGARTICLEChimericAntigenReceptor-EngineeredTCellsfortheTreatmentofMetastaticProstateCancer11VictoriaHillerdal•MagnusEssandÓTheAuthor(s)2015.ThisarticleispublishedwithopenaccessatSpringerlink.comAbstractCancerimmunotherapywasselectedast

2、heinhibitorsthatcanreducetumorimmunosuppressionmayBreakthroughoftheYear2013bytheeditorsofScience,inhelpimproveefficacy.Otherelegantapproachessuchaspartbecauseofthesuccessfultreatmentofrefractoryhe-inducedexpressionofimmunestimulatorycytokinesuponmatologicalmalignancieswithadop

3、tivetransferofchi-targetrecognitionmayalsohelptorecruitothereffectormericantigenreceptor(CAR)-engineeredTcells.Effectiveimmunecellstometastaticsites.AlthoughtoxicitiesaretreatmentofBcellleukemiamaypavetheroadtofuturedifficulttopredictinprostatecancer,severeon-target/off-treatm

4、entofsolidtumors,usingsimilarapproaches.Thetumortoxicitieshavebeenobservedinclinicaltrialswithprostateexpressesmanyuniqueproteinsand,sincetheuseofCARTcellsagainsthematologicalmalignancies;prostateglandisadispensableorgan,CARTcellscantherefore,thechoiceofthetargetantigenisgoin

5、gtobepotentiallybeusedtotargetthesetissue-specificantigens.crucial.Thisreviewfocusesondifferentmeansofac-However,thelocationandcompositionofprostatecancercomplishingmaximaleffectivenessofCARTcelltherapymetastasescomplicatethetaskoftreatingthesetumors.Itforprostatecancerbonemet

6、astaseswhileminimizingsideisthereforelikelythatmoresophisticatedCARTcellap-effectsandCARTcell-associatedtoxicities.CARTcell-proachesaregoingtoberequiredforprostatemetastasisbasedtherapiesforprostatecancerhavethepotentialtobethanforBcellmalignancies.Twomainchallengesthatathera

7、pymodelforothersolidtumors.needtoberesolvedarehowtoincreasethemigrationandinfiltrationofCARTcellsintoprostatecancerbonemetastasesandhowtocounteracttheimmunosuppressive1AdoptiveCARTCellTherapymicroenvironmentfoundinbonelesions.Inclusionofhoming(chemokine)receptorsinCARTcellsmay

8、im-TheuseofTcellstotreatsolidtumorswasinitiallyre-provetheirrecruitm