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| Home > Publications database > Hexokinase2-engineered T cells display increased anti-tumor function. |
| Home > Publications database > Hexokinase2-engineered T cells display increased anti-tumor function. |
| Journal Article | DKFZ-2025-00705 |
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2025
Frontiers Media
Lausanne
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Please use a persistent id in citations: doi:10.3389/fimmu.2025.1477929
Abstract: T cells face significant metabolic challenges in the tumor microenvironment (TME), where cancer cells monopolize critical nutrients like glucose and amino acids. This metabolic competition supports tumor growth while impairing T-cell anti-tumor responses, partly by reducing glycolytic function. Hexokinase 2 (HK2), a key enzyme in glycolysis, plays a pivotal role in maintaining T-cell functionality.To enhance T-cell function, primary human T cells were genetically engineered to overexpress HK2 alongside a tumor-specific receptor. These engineered T cells were tested in vitro and in vivo to evaluate their metabolic and therapeutic efficacy.HK2-engineered T cells exhibited increased glycolytic capacity, leading to enhanced cytokine secretion, activation marker expression, and metabolic activity compared to controls. In vivo studies using a human tumor xenograft model demonstrated the superior therapeutic efficacy of HK2-engineered T cells, including delayed tumor growth and improved survival.HK2 overexpression improves T-cell metabolic fitness and functionality in hostile TMEs, offering a promising foundation for the development of next-generation immunotherapies targeting T-cell metabolism.
Keyword(s): Hexokinase: genetics (MeSH) ; Hexokinase: metabolism (MeSH) ; Hexokinase: immunology (MeSH) ; Humans (MeSH) ; Animals (MeSH) ; T-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; T-Lymphocytes: transplantation (MeSH) ; Mice (MeSH) ; Tumor Microenvironment: immunology (MeSH) ; Xenograft Model Antitumor Assays (MeSH) ; Cell Line, Tumor (MeSH) ; Glycolysis (MeSH) ; Immunotherapy, Adoptive: methods (MeSH) ; Neoplasms: immunology (MeSH) ; Neoplasms: therapy (MeSH) ; Neoplasms: metabolism (MeSH) ; Cytokines: metabolism (MeSH) ; Lymphocyte Activation (MeSH) ; Female (MeSH) ; T-cells ; TCR ; cellular immunotherapy ; hexokinase 2 ; immunometabolism ; Hexokinase ; HK2 protein, human ; Cytokines
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