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Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.
Li, Yan-Ruide; Zhou, Yang; Yu, Jiaji; Kim, Yu Jeong; Li, Miao; Lee, Derek; Zhou, Kuangyi; Chen, Yuning; Zhu, Yichen; Wang, Yu-Chen; Li, Zhe; Yu, Yanqi; Dunn, Zachary Spencer; Guo, Wenbin; Cen, Xinjian; Husman, Tiffany; Bajpai, Aarushi; Kramer, Adam; Wilson, Matthew; Fang, Ying; Huang, Jie; Li, Shuo; Zhou, Yonggang; Zhang, Yuchong; Hahn, Zoe; Zhu, Enbo; Ma, Feiyang; Pan, Calvin; Lusis, Aldons J; Zhou, Jin J; Seet, Christopher S; Kohn, Donald B; Wang, Pin; Zhou, Xianghong Jasmine; Pellegrini, Matteo; Puliafito, Benjamin R; Larson, Sarah M; Yang, Lili.
Afiliación
  • Li YR; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhou Y; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Yu J; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Kim YJ; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Li M; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Lee D; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhou K; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Chen Y; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhu Y; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Wang YC; Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Li Z; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Yu Y; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Dunn ZS; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA.
  • Guo W; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA.
  • Cen X; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Husman T; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Bajpai A; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Kramer A; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Wilson M; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Fang Y; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Huang J; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Li S; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhou Y; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhang Y; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Hahn Z; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhu E; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Ma F; Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Pan C; Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Lusis AJ; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhou JJ; Department of Medicine, Division of Cardiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Seet CS; Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Kohn DB; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
  • Wang P; Eli and Edythe Broad Centre of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
  • Zhou XJ; Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, Los Angeles, CA, USA.
  • Pellegrini M; Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Puliafito BR; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
  • Larson SM; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
  • Yang L; Eli and Edythe Broad Centre of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
Nat Biotechnol ; 2024 May 14.
Article en En | MEDLINE | ID: mdl-38744947
ABSTRACT
Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.
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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2024 Tipo del documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2024 Tipo del documento: Article