| Autor: |
Raul Vizcardo, Nicholas D. Klemen, S.M. Rafiqul Islam, Devikala Gurusamy, Naritaka Tamaoki, Daisuke Yamada, Haruhiko Koseki, Benjamin L. Kidder, Zhiya Yu, Li Jia, Amanda N. Henning, Meghan L. Good, Marta Bosch-Marce, Takuya Maeda, Chengyu Liu, Zied Abdullaev, Svetlana Pack, Douglas C. Palmer, David F. Stroncek, Fumito Ito, Francis A. Flomerfelt, Michael J. Kruhlak, Nicholas P. Restifo |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 22, Iss 12, Pp 3175-3190 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2018.02.087 |
| Popis: |
Summary: Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs). iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies. : A barrier for clinical application of iPSC-derived CD8 T cells using OP9/DLL1 is their abnormal biology. Vizcardo et al. show that a 3D thymic culture system enables the generation of a homogeneous antigen-specific T cell subset, named iTEs, which closely mimics naive T cells and exhibits potent anti-tumor activity. Keywords: thymopoiesis, T cell differentiation, iPSC differentiation, adoptive cell transfer, naïve T cell, recent rhymic emigrants, fetal thymus organ culture, immunotherapy, 3D culture, tumor antigen specific T cell |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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