| Literature DB >> 29562175 |
Raul Vizcardo1, Nicholas D Klemen2, S M Rafiqul Islam2, Devikala Gurusamy2, Naritaka Tamaoki2, Daisuke Yamada3, Haruhiko Koseki3, Benjamin L Kidder4, Zhiya Yu2, Li Jia5, Amanda N Henning2, Meghan L Good2, Marta Bosch-Marce2, Takuya Maeda2, Chengyu Liu6, Zied Abdullaev7, Svetlana Pack7, Douglas C Palmer2, David F Stroncek8, Fumito Ito9, Francis A Flomerfelt10, Michael J Kruhlak11, Nicholas P Restifo12.
Abstract
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.Entities:
Keywords: 3D culture; T cell differentiation; adoptive cell transfer; fetal thymus organ culture; iPSC differentiation; immunotherapy; naïve T cell; recent rhymic emigrants; thymopoiesis; tumor antigen specific T cell
Mesh：
Year: 2018 PMID： 29562175 PMCID： PMC5930030 DOI： 10.1016/j.celrep.2018.02.087
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423