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Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System.
Vizcardo, Raul; Klemen, Nicholas D; Islam, S M Rafiqul; Gurusamy, Devikala; Tamaoki, Naritaka; Yamada, Daisuke; Koseki, Haruhiko; Kidder, Benjamin L; Yu, Zhiya; Jia, Li; Henning, Amanda N; Good, Meghan L; Bosch-Marce, Marta; Maeda, Takuya; Liu, Chengyu; Abdullaev, Zied; Pack, Svetlana; Palmer, Douglas C; Stroncek, David F; Ito, Fumito; Flomerfelt, Francis A; Kruhlak, Michael J; Restifo, Nicholas P.
Afiliação
  • Vizcardo R; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: vizcardo@nih.gov.
  • Klemen ND; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Islam SMR; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Gurusamy D; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Tamaoki N; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Yamada D; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa 230-0045, Japan.
  • Koseki H; Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa 230-0045, Japan.
  • Kidder BL; Department of Oncology and Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
  • Yu Z; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Jia L; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Henning AN; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Good ML; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Bosch-Marce M; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Maeda T; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Liu C; Transgenic Core, Division of Intramural Research, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
  • Abdullaev Z; Experimental Pathology Laboratory, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Pack S; Experimental Pathology Laboratory, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Palmer DC; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Stroncek DF; Department of Transfusion Medicine Department, Clinical Center, NIH, Bethesda, MD 20892, USA.
  • Ito F; Department of Surgical Oncology, Roswell Park Cancer Center, Buffalo, NY 14263, USA; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
  • Flomerfelt FA; Experimental Transplantation and Immunology Branch, NIH Clinical Center, NIH, Bethesda, MD 20892, USA.
  • Kruhlak MJ; Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Restifo NP; Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: restifo@nih.gov.
Cell Rep ; 22(12): 3175-3190, 2018 03 20.
Article em En | MEDLINE | ID: mdl-29562175
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 CD8αß+ 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Timo / Imageamento Tridimensional / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Timo / Imageamento Tridimensional / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article