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 sti...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.展开更多
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).
文摘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.
