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From pluripotent stem cells to T cells.

作者信息

Montel-Hagen Amélie, Crooks Gay M

机构信息

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA; Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA; Broad Stem Cell Research Center, University of California, Los Angeles, CA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA.

出版信息

Exp Hematol. 2019 Mar;71:24-31. doi: 10.1016/j.exphem.2018.12.001. Epub 2018 Dec 24.


DOI:10.1016/j.exphem.2018.12.001
PMID:30590093
Abstract

The generation of T cells from human pluripotent stem cells (PSCs) opens a valuable experimental window into developmental hematopoiesis and raises the possibility of a new therapeutic approach for T-cell immunotherapy. After directing PSCs through mesoderm and early hematopoietic developmental stages, commitment to the T-cell lineage has been achieved by several groups using coculture with stromal cells that express a notch ligand, recapitulating the critical signals that initiate the first stages of normal T-cell differentiation in the thymus. However, positive selection and the production of mature T cells from human PSCs have been limited to date. Nonetheless, T-lineage cells have been generated from PSCs with tumor antigen specificity either through a prearranged clonal T-cell receptor (TCR) or lentiviral-mediated expression of chimeric antigen receptors. The recent development of a 3D artificial organoid model has demonstrated that PSCs can generate mature conventional T cells that are fully functional and express a diverse TCR repertoire. Introduction of a transgenic TCR at the PSC stage allows for the production of tumor-antigen-specific, mature conventional T cells. The tools of gene editing in PSCs are ideally suited to produce off-the-shelf universal products for T-cell immunotherapy. In this review, we describe the studies that have led to this exciting moment in PSC biology and discuss translation to clinical applications.

摘要

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引用本文的文献

[1]
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Int J Cancer. 2025-11-1

[2]
Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.

STAR Protoc. 2025-3-21

[3]
Rediscovering the human thymus through cutting-edge technologies.

J Exp Med. 2024-10-7

[4]
Optimizing in vitro T cell differentiation by using induced pluripotent stem cells with GFP-RUNX1 and mCherry-TCF7 labelling.

Cell Prolif. 2024-10

[5]
Lineage-tracing hematopoietic stem cell origins in vivo to efficiently make human HLF+ HOXA+ hematopoietic progenitors from pluripotent stem cells.

Dev Cell. 2024-5-6

[6]
The Emerging Role of Induced Pluripotent Stem Cells as Adoptive Cellular Immunotherapeutics.

Biology (Basel). 2023-11-11

[7]
Strength of CAR signaling determines T cell versus ILC differentiation from pluripotent stem cells.

Cell Rep. 2023-3-28

[8]
Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).

Int J Mol Sci. 2023-2-3

[9]
Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.

Cells Tissues Organs. 2023

[10]
Generation of Retrogenic Mice to Investigate T Cell Development.

Methods Mol Biol. 2023

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