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Click CAR-T cell engineering for robustly boosting cell immunotherapy in blood and subcutaneous xenograft tumor

查看全文 作  者:Hong [1,2]Pan;Wenjun [1]Li;Ze [1]Chen;Yingmei [1]Luo;Wei [1]He;Mengmeng [1]Wang;Xiaofan [1]Tang;Huamei [1]He;Lanlan [1,2]Liu;Mingbin [1]Zheng;Xin [1]Jiang;Ting [1]Yin;Ruijing [1]Liang;Yifan [1,2]Ma;Lintao [1]Cai 高影响力作者 机构地区:[1]Guangdong Key Laboratory of Nanomedicine,CAS-HK Joint Lab of Biomaterials,CAS Key Lab for Health Informatics,Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations,Shenzhen Institutes of Advanced Technology(SIAT),Chinese Academy of Sciences,Shenzhen,518055,PR China;[2]HRYZ Biotech Co.,Shenzhen,518057,PR China高影响力机构 出  处:《Bioactive Materials》索引2021年第6卷第4期,共12页高影响力期刊 基  金:the National Natural Science Foundation of China(Grant No.81971749,81601552,31571013);Guangdong Natural Science Foundation of Research Team(2016A030312006);Shenzhen Science and Technology Program(JCYJ20170818163739458,JCYJ20170306160217433,CYZZ20170331150956189). 摘  要:The adoptive transfer of chimeric antigen receptor-T(CAR-T)cells has shown remarkable clinical responses in hematologic malignancies.However,unsatisfactory curative results and side effects for tumor treatment are still unsolved problems.Herein we develop a click CAR-T cell engineering strategy via cell glycometabolic labeling for robustly boosting their antitumor effects and safety in vivo.Briefly,paired chemical groups(N3/BCN)are separately incorporated into CAR-T cell and tumor via nondestructive intrinsic glycometabolism of exogenous Ac4GalNAz and Ac4ManNBCN,serving as an artificial ligand-receptor.Functional groups anchored on cell surface strengthen the interaction of CAR-T cell and tumor via bioorthogonal click chemistry,further enhancing specific recognition,migration and selective antitumor effects of CAR-T cells.In vivo,click CAR-T cell completely removes lymphoma cells and minimizes off-target toxicity via selective and efficient bioorthogonal targeting in blood cancer.Surprisingly,compared to unlabeled cells,artificial bioorthogonal targeting significantly promotes the accumulation,deep penetration and homing of CAR-T cells into tumor tissues,ultimately improving its curative effect for solid tumor.Click CAR-T cell engineering robustly boosts selective recognition and antitumor capabilities of CAR T cells in vitro and in vivo,thereby holding a great potential for effective clinical cell immunotherapy with avoiding adverse events in patients. 关 键 词:CAR-T cell Bioorthogonal click chemistry Glycometabolic labeling Off-target effects Cell immunotherapy
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