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1、·568·中國(guó)實(shí)驗(yàn)血液學(xué)雜志JournalofExperimentalHematology2015;23(2):568-572文章編號(hào)(ArticleID):1009-2137(2015)02-0568-05·綜述·嵌合抗原受體修飾的CAR-T/NK細(xì)胞在多發(fā)性骨髓瘤治療中的應(yīng)用1,222*王蕾,歐劍鋒,白海1蘭州大學(xué)第二臨床醫(yī)學(xué)院血液科,甘肅蘭州730050;2蘭州軍區(qū)蘭州總醫(yī)院血液科,全軍血液病中心,甘肅蘭州730050;摘要嵌合抗原受體(chimericantigenreceptor,CAR)是一
2、種合成跨膜蛋白,通過抗腫瘤細(xì)胞上的特異性或相關(guān)性抗原來重新定向被修飾的細(xì)胞。CAR修飾的T/NK細(xì)胞,特別是CAR-T細(xì)胞是近年來迅速發(fā)展的腫瘤過繼免疫治療新手段,它賦予T/NK細(xì)胞靶向殺傷活性,并可克服腫瘤局部免疫抑制微環(huán)境和打破宿主免疫耐受狀態(tài)。CAR將識(shí)別腫瘤相關(guān)抗原的單鏈抗體和T/NK細(xì)胞的活化基序相結(jié)合,通過基因轉(zhuǎn)導(dǎo)賦予T/NK細(xì)胞腫瘤靶向性、更強(qiáng)的殺傷活性和持久的生命力。本文就CAR發(fā)展、CAR-T和CAR-NK細(xì)胞的比較、MM細(xì)胞的表面標(biāo)記和CAR在MM中的應(yīng)用及CAR-T/NK細(xì)胞的前景
3、進(jìn)行綜述。關(guān)鍵詞多發(fā)性骨髓瘤;嵌合抗原受體;過繼免疫治療中圖分類號(hào)R733.3文獻(xiàn)標(biāo)識(shí)碼Adoi:10.7534/j.issn.1009-2137.2015.02.053ApplicationofChimericAntigenReceptor-ModifiedCAR-T/NKCellstoTreatmentofMultipleMyeloma———Review1,222*WANGLei,OUjian-Feng,BAIHai1DepartmentofHematology,ThesecondClinicalM
4、edicalCollege,LanzhouUniversity,Lanzhou730050,GansuProvince,China;2DepartmentofHematology,CenterofHematologicDiseasesofChinesePLA;LanzhouMilitaryCommandGeneralHospital,Lanzhou730050,GansuProvince,China*CorrespondingAuthor:BAIHai,SeniorPhysician,TutorofMa
5、sterPostgraduate.E-mail:baihai98@tom.comAbstractChimericantigenreceptor(CAR)isasynthesizedtransmembraneprotein,whichredirectsthemodifiedcellsthroughspecificorassociatedantigenontumorcells.CAR-modifiedT/NKcells,especiallyCAR-Tcells,areanewtoolofrapidlydev
6、elopingofadoptiveimmunotherapyoftumorinrecentyears,theygiveT/NKcellsthetargetingcytotoxicactivityandcanovercomethetumorimmunosuppressivemicroenvironmentandbreakthestateofthehostimmunetolerance.CARcombinesthesingle-chainantibodytotumor-associatedantigenwi
7、thT/NKcells'activatedmotifs,givingT/NKcells'tumortargetingactivity,soenhancingtheircytotoxicactivityandlastingthevitalitybygenetransduction.InthisarticletheCARdevelopment,comparisonofCAR-TandCAR-NKcells,surfacemarkersonMMcellsanduseofCARinMM,andCARperspe
8、ctivesaresummarized.Keywordsmultiplemyeloma;chimericantigenreceptor;adoptiveimmunotherapyJExpHematol2015;(2):568-572[2]多發(fā)性骨髓瘤(multiplemyeloma,MM)是一種病。無論是初次診斷的MM、復(fù)發(fā)難治性MM,還以異常漿細(xì)胞增生導(dǎo)致的單克隆免疫球蛋白聚集為是已行造血干細(xì)胞移植的患者,均可應(yīng)用CAR進(jìn)行[3]特征的惡