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Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.
Zhu, Yanni; Smith, Drake J; Zhou, Yang; Li, Yan-Ruide; Yu, Jiaji; Lee, Derek; Wang, Yu-Chen; Di Biase, Stefano; Wang, Xi; Hardoy, Christian; Ku, Josh; Tsao, Tasha; Lin, Levina J; Pham, Alexander T; Moon, Heesung; McLaughlin, Jami; Cheng, Donghui; Hollis, Roger P; Campo-Fernandez, Beatriz; Urbinati, Fabrizia; Wei, Liu; Pang, Larry; Rezek, Valerie; Berent-Maoz, Beata; Macabali, Mignonette H; Gjertson, David; Wang, Xiaoyan; Galic, Zoran; Kitchen, Scott G; An, Dong Sung; Hu-Lieskovan, Siwen; Kaplan-Lefko, Paula J; De Oliveira, Satiro N; Seet, Christopher S; Larson, Sarah M; Forman, Stephen J; Heath, James R; Zack, Jerome A; Crooks, Gay M; Radu, Caius G; Ribas, Antoni; Kohn, Donald B; Witte, Owen N; Yang, Lili.
Afiliación
  • Zhu Y; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Smith DJ; 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.
  • Li YR; Department of Microbiology, Immunology & Molecular Genetics, 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.
  • Lee D; 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.
  • Di Biase 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.
  • Hardoy C; 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.
  • Lin LJ; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Pham AT; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Moon H; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • McLaughlin J; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Cheng D; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hollis RP; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Campo-Fernandez B; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Urbinati F; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wei L; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Ahmanson Translational Imaging Division, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Pang L; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Ahmanson Translational Imaging Division, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Rezek V; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Berent-Maoz B; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Macabali MH; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Gjertson D; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wang X; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Galic Z; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kitchen SG; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • An DS; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; School of Nursing, University of California, Los Angeles, Los Angeles, CA 90095, USA; AIDS Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hu-Lieskovan S; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Kaplan-Lefko PJ; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • De Oliveira SN; Department of Pediatrics, 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; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Larson SM; Department of Internal Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Forman SJ; Hematological Malignancies and Hematopoietic Stem Cell Transplantation Institute, City of Hope, Duarte, CA 91010, USA.
  • Heath JR; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Zack JA; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine,
  • Crooks GM; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, Dav
  • Radu CG; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Ahmanson Translational Imaging Division, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, Unive
  • Ribas A; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, Da
  • Kohn DB; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics
  • Witte ON; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Ca
  • Yang L; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Ca
Cell Stem Cell ; 25(4): 542-557.e9, 2019 10 03.
Article en En | MEDLINE | ID: mdl-31495780
ABSTRACT
Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide therapeutic levels of iNKT cells for a patient's lifetime. Using a human HSC engrafted mouse model and a human iNKT TCR gene engineering approach, we demonstrated the efficient and long-term generation of HSC-iNKT cells in vivo. These HSC-iNKT cells closely resembled endogenous human iNKT cells, could deploy multiple mechanisms to attack tumor cells, and effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models. Preclinical safety studies showed no toxicity or tumorigenicity of the HSC-iNKT cell therapy. Collectively, these results demonstrated the feasibility, safety, and cancer therapy potential of the proposed HSC-iNKT cell therapy and laid a foundation for future clinical development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Inmunoterapia Adoptiva / Células T Asesinas Naturales / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Inmunoterapia Adoptiva / Células T Asesinas Naturales / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos