Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells
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Published:2022-05-14
Issue:1
Volume:11
Page:
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ISSN:2162-3619
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Container-title:Experimental Hematology & Oncology
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language:en
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Short-container-title:Exp Hematol Oncol
Author:
Guo Rongqun,Li Wei,Li Yadan,Li Yingmei,Jiang Zhongxing,Song Yongping
Abstract
AbstractEngineered T cells have been shown to be highly effective in cancer immunotherapy, although T cell exhaustion presents a challenge for their long-term function. Additional T-cell sources must be exploited to broaden the application of engineered T cells for immune defense and reconstitution. Unlimited sources of pluripotent stem cells (PSCs) have provided a potential opportunity to generate precise-engineered therapeutic induced T (iT) cells. Single-cell transcriptome analysis of PSC-derived induced hematopoietic stem and progenitor cells (iHSPC)/iT identified the developmental pathways and possibilities of generating functional T cell from PSCs. To date, the PSC-to-iT platforms encounter several problems, including low efficiency of conventional T subset specification, limited functional potential, and restrictions on large-scale application, because of the absence of a thymus-like organized microenvironment. The updated PSC-to-iT platforms, such as the three-dimensional (3D) artificial thymic organoid (ATO) co-culture system and Runx1/Hoxa9-enforced iT lymphopoiesis, provide fresh perspectives for coordinating culture conditions and transcription factors, which may greatly improve the efficiency of T-cell generation greatly. In addition, the improved PSC-to-iT platform coordinating gene editing technologies will provide various functional engineered unconventional or conventional T cells. Furthermore, the clinical applications of PSC-derived immune cells are accelerating from bench to bedside.
Funder
National Natural Science Foundation of China China Postdoctoral Science Foundation the Key scientific research projects of colleges and universities in Henan Province the Postdoctoral Research Start-up Funding of Henan Province Provincial and Ministry Joint Co-construction Project of Henan Medical Science and Technology Research Plan Joint Co-construction Project of Henan Medical Science and Technology Research Plan
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Hematology
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