ArticleCell stem cell2019
Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.
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Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66citing papers in PubMed
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Who cites it
66 citing papers in PubMed.
- Scalable generation of hematopoietic stem cell-engineered off-the-shelf mono-specific cytotoxic T cells targeting solid tumors.Cell reports. Medicine · 2026Article
- Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.Signal transduction and targeted therapy · 2026Review
- Experimental models in immuno-oncology and their translational impact.Discover oncology · 2026Review
- Exploring CAR cell therapies beyond CAR-T for myeloid malignancies.Journal of biomedical science · 2026Review
- Natural Killer T Cell Function in Lymphoma Patients.Biomolecules · 2026Article
- Article
- Nonclassical MHC-I Molecules: Emerging Therapeutic Targets in Next-Generation Immunotherapy.MedComm · 2026Review
- Innovative approaches in the treatment of hematologic malignancies: the role of CRISPR-engineered microbiomes along the gut-immune axis in immunotherapy development.Cancer cell international · 2026Review
- Article
- Innate-like T Cell Biology in the Tumor Microenvironment Implications for Cancer Immunotherapy.Cells · 2026Review
- Stem cell engineering for the generation of allogeneic CAR-directed natural killer T cells targeting endometrial carcinoma.Experimental hematology & oncology · 2026Article
- Rejuvenated Hematopoietic Stem and Progenitor Cell-Engineered CAR-Armored Natural Killer T Cells for Malignant Pleural Mesothelioma.Research (Washington, D.C.) · 2026Article
- Allogeneic stem cell-engineered EGFRvIII-specific CAR-NKT cells for treating glioblastoma with enhanced efficacy and safety.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting triple-negative breast cancer using cord-blood CD34⁺ HSPC-derived mesothelin-specific CAR-NKT cells with potent antitumor activity.Journal of hematology & oncology · 2025Article
- Engineering adoptive cell therapy for solid tumors.Medical oncology (Northwood, London, England) · 2025Review
- Multimodal targeting of metastatic renal cell carcinoma via CD70-directed allogeneic CAR-NKT cells.Cell reports. Medicine · 2025Article
- Comparative efficacy and safety of PSCA CAR-engineered Vδ1 γδ T cells for immunotherapy of pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny.Nature communications · 2025Article
- Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects.Journal of hematology & oncology · 2025Review
- Managing allorejection in off-the-shelf CAR-engineered cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
44 authors.
Yanni ZhuDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Drake J SmithDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yang ZhouDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yan-Ruide LiDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jiaji YuDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Derek LeeDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yu-Chen WangDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Stefano Di BiaseDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xi WangDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Christian HardoyDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Josh KuDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Tasha TsaoDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Levina J LinDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Alexander T PhamDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Heesung MoonDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jami McLaughlinDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Donghui ChengDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Roger P HollisDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Beatriz Campo-FernandezDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Fabrizia UrbinatiDepartment of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Liu WeiDepartment 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.
Larry PangDepartment 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.
Valerie RezekEli 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.
Beata Berent-MaozDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mignonette H MacabaliDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David GjertsonDepartment 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.
Xiaoyan WangDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Zoran GalicEli 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.
Scott G KitchenEli 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.
Dong Sung AnDepartment 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.
Siwen Hu-LieskovanDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Paula J Kaplan-LefkoDepartment 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.
Satiro N De OliveiraDepartment of Pediatrics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Christopher S SeetEli 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.
Sarah M LarsonDepartment of Internal Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Stephen J FormanHematological Malignancies and Hematopoietic Stem Cell Transplantation Institute, City of Hope, Duarte, CA 91010, USA.
James R HeathInstitute for Systems Biology, Seattle, WA 98109, USA.
Jerome A ZackDepartment 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, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gay M CrooksEli 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, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Caius G RaduDepartment 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, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Antoni RibasDepartment 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, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Donald B KohnDepartment 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, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Owen N WitteDepartment 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 Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Lili YangDepartment 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 Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: liliyang@ucla.edu.
Funding
Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5MUCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2MTUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gay M Crooks, David A. Nathanson · 1985 to 2026
$10.5MStem Cell-Engineered Invariant Natural Killer T Cells for Cancer TherapyDP2CA196335 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, LILI · 2014 to 2014
$2.3MEngineering Precision Medicine to Enhance Graft-Versus-Lymphoma EffectK23CA222659 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DE OLIVEIRA, SATIRO NAKAMURA · 2017 to 2022
$920kNCI NIH HHS DP2 CA196335NCI NIH HHS K23 CA222659NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS T32 CA009056
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.
Indexed as
AnimalsCells, CulturedGenetic EngineeringHematopoietic Stem CellsHumansImmunotherapy, AdoptiveMiceMice, SCIDNatural Killer T-CellsNeoplasmsReceptors, Antigen, T-CellXenograft Model Antitumor AssaysReceptors, Antigen, T-Cellcancer immunotherapycell therapygene therapyhematopoietic stem cellHSCHSCTHSC transferiNKTinvariant natural killer T cellpreclinical developmentsr39TK suicide genestem cell therapyT cell receptorTCR
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