αβ-T cell receptor transduction gives superior mitochondrial function to γδ-T cells with promising persistence
© 2023 The Authors..
Adoptive cell therapy using allogeneic γδ-T cells is a promising option for off-the-shelf T cell products with a low risk of graft-versus-host disease (GVHD). Long-term persistence may boost the clinical development of γδ-T cell products. In this study, we found that genetically modified Vγ9+Vδ2+ T cells expressing a tumor antigen-specific αβ-TCR and CD8 coreceptor (GMC) showed target-specific killing and excellent persistence. To determine the mechanisms underlying these promising effects, we investigated metabolic characteristics. Cytokine secretion by γδ-TCR-stimulated nongene-modified γδ-T cells (NGMCs) and αβ-TCR-stimulated GMCs was equally suppressed by a glycolysis inhibitor, although the cytokine secretion of αβ-TCR-stimulated GMCs was more strongly inhibited by ATP synthase inhibitors than that of γδ-TCR-stimulated NGMCs. Metabolomic and transcriptomic analyses, flow cytometry analysis using mitochondria-labeling dyes and extracellular flux analysis consistently suggest that αβ-TCR-transduced γδ-T cells acquire superior mitochondrial function. In conclusion, αβ-TCR-transduced γδ-T cells acquire superior mitochondrial function with promising persistence.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
iScience - 26(2023), 10 vom: 20. Okt., Seite 107802 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ishihara, Mikiya [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 20.09.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2023.107802 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362169683 |
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| 520 | |a © 2023 The Authors. | ||
| 520 | |a Adoptive cell therapy using allogeneic γδ-T cells is a promising option for off-the-shelf T cell products with a low risk of graft-versus-host disease (GVHD). Long-term persistence may boost the clinical development of γδ-T cell products. In this study, we found that genetically modified Vγ9+Vδ2+ T cells expressing a tumor antigen-specific αβ-TCR and CD8 coreceptor (GMC) showed target-specific killing and excellent persistence. To determine the mechanisms underlying these promising effects, we investigated metabolic characteristics. Cytokine secretion by γδ-TCR-stimulated nongene-modified γδ-T cells (NGMCs) and αβ-TCR-stimulated GMCs was equally suppressed by a glycolysis inhibitor, although the cytokine secretion of αβ-TCR-stimulated GMCs was more strongly inhibited by ATP synthase inhibitors than that of γδ-TCR-stimulated NGMCs. Metabolomic and transcriptomic analyses, flow cytometry analysis using mitochondria-labeling dyes and extracellular flux analysis consistently suggest that αβ-TCR-transduced γδ-T cells acquire superior mitochondrial function. In conclusion, αβ-TCR-transduced γδ-T cells acquire superior mitochondrial function with promising persistence | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cellular therapy | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Molecular biology | |
| 700 | 1 | |a Miwa, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Fujiwara, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Akahori, Yasushi |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Takuma |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Yoshimasa |e verfasserin |4 aut | |
| 700 | 1 | |a Tawara, Isao |e verfasserin |4 aut | |
| 700 | 1 | |a Shiku, Hiroshi |e verfasserin |4 aut | |
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