T cells play essential roles in antitumor therapy.Via gene engineering technique to enhance tumor-antigen specificity,patient peripheral blood-derived T cells(PBT)show encouraging clinical outcomes in treating certain...T cells play essential roles in antitumor therapy.Via gene engineering technique to enhance tumor-antigen specificity,patient peripheral blood-derived T cells(PBT)show encouraging clinical outcomes in treating certain blood malignancies.However,the high costs,functionality exhaustion,and disease-condition-dependent availability of PBT prompt the attempts of exploring alternative T cell sources.Theoretically,induced T cells from pluripotent stem cells(PSC)are ideal candidates that integrate plenty of advantages that primary T cells lack,including unlimited off-the-shelf cell source and precision gene editing feasibility.However,researchers are still struggling with developing a straightforward protocol to induce functional and immunocompetent human T cells from PSC.Based on stromal cell-expressing or biomaterial-presenting Notch ligands DLL1 or DLL4,natural and induced blood progenitors can differentiate further toward T lineage commitment.However,none of the reported T induction protocols has yet translated into any clinical application,signaling the existence of numerous technical barriers for regenerating T cells functionally matching their natural PBT counterparts.Alternatively,new approaches have been developed to repopulate induced T lymphopoiesis via in vivo reprogramming or transplanting induced T cell precursors.Here,we review the most recent progress in the T cell regeneration field,and the remaining challenges dragging their clinical applications.展开更多
基金supported by the Key R&D program from Ministry of Science and Technology of China(2019YFA0110203)Major Research and Development Project of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104006)+2 种基金the Health and Medical Care Collaborative Innovation Program of Guangzhou Scientific and Technology(201803040017)the Science and Technology Planning Project of Guangdong Province(2017B030314056)the National Natural Science Foundation of China(31471117,81470281,31600948).
文摘T cells play essential roles in antitumor therapy.Via gene engineering technique to enhance tumor-antigen specificity,patient peripheral blood-derived T cells(PBT)show encouraging clinical outcomes in treating certain blood malignancies.However,the high costs,functionality exhaustion,and disease-condition-dependent availability of PBT prompt the attempts of exploring alternative T cell sources.Theoretically,induced T cells from pluripotent stem cells(PSC)are ideal candidates that integrate plenty of advantages that primary T cells lack,including unlimited off-the-shelf cell source and precision gene editing feasibility.However,researchers are still struggling with developing a straightforward protocol to induce functional and immunocompetent human T cells from PSC.Based on stromal cell-expressing or biomaterial-presenting Notch ligands DLL1 or DLL4,natural and induced blood progenitors can differentiate further toward T lineage commitment.However,none of the reported T induction protocols has yet translated into any clinical application,signaling the existence of numerous technical barriers for regenerating T cells functionally matching their natural PBT counterparts.Alternatively,new approaches have been developed to repopulate induced T lymphopoiesis via in vivo reprogramming or transplanting induced T cell precursors.Here,we review the most recent progress in the T cell regeneration field,and the remaining challenges dragging their clinical applications.
