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Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy.
Li, Yan-Ruide; Zhou, Yang; Kim, Yu Jeong; Zhu, Yanni; Ma, Feiyang; Yu, Jiaji; Wang, Yu-Chen; Chen, Xianhui; Li, Zhe; Zeng, Samuel; Wang, Xi; Lee, Derek; Ku, Josh; Tsao, Tasha; Hardoy, Christian; Huang, Jie; Cheng, Donghui; Montel-Hagen, Amélie; Seet, Christopher S; Crooks, Gay M; Larson, Sarah M; Sasine, Joshua P; Wang, Xiaoyan; Pellegrini, Matteo; Ribas, Antoni; Kohn, Donald B; Witte, Owen; Wang, Pin; Yang, Lili.
Affiliation
  • Li YR; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Zhou Y; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kim YJ; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Zhu Y; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ma F; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Yu J; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wang YC; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Chen X; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
  • Li Z; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Zeng S; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wang X; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Lee D; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ku J; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Tsao T; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hardoy C; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Huang J; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Cheng D; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Montel-Hagen A; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Seet CS; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Crooks GM; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Larson SM; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Sasine JP; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wang X; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Pellegrini M; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ribas A; Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kohn DB; Department of Internal Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Witte O; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wang P; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Yang L; Division of Hematology/Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell Rep Med ; 2(11): 100449, 2021 11 16.
Article in En | MEDLINE | ID: mdl-34841295
ABSTRACT
Cell-based immunotherapy has become the new-generation cancer medicine, and "off-the-shelf" cell products that can be manufactured at large scale and distributed readily to treat patients are necessary. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing allogeneic cell therapy because they are powerful immune cells targeting cancers without graft-versus-host disease (GvHD) risk. However, healthy donor blood contains extremely low numbers of endogenous iNKT cells. Here, by combining hematopoietic stem cell (HSC) gene engineering and in vitro differentiation, we generate human allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells at high yield and purity; these cells closely resemble endogenous iNKT cells, effectively target tumor cells using multiple mechanisms, and exhibit high safety and low immunogenicity. These cells can be further engineered with chimeric antigen receptor (CAR) to enhance tumor targeting or/and gene edited to ablate surface human leukocyte antigen (HLA) molecules and further reduce immunogenicity. Collectively, these preclinical studies demonstrate the feasibility and cancer therapy potential of AlloHSC-iNKT cell products and lay a foundation for their translational and clinical development.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematopoietic Stem Cells / Natural Killer T-Cells / Cell Engineering / Allogeneic Cells / Immunotherapy / Neoplasms Limits: Animals / Humans Language: En Journal: Cell Rep Med Year: 2021 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematopoietic Stem Cells / Natural Killer T-Cells / Cell Engineering / Allogeneic Cells / Immunotherapy / Neoplasms Limits: Animals / Humans Language: En Journal: Cell Rep Med Year: 2021 Document type: Article Affiliation country: United States