%0 Journal Article
%A Zur, Raphaëlle Toledano
%A Zurinam, Shiran Didi
%A Radman, Maria
%A Funaro Balouka, Elia
%A Borodianskiy-Shteinberg, Tatiana
%A Saur, Dieter
%A Cohen, Cyrille J
%T Hexokinase2-engineered T cells display increased anti-tumor function.
%J Frontiers in immunology
%V 16
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DKFZ-2025-00705
%P 1477929
%D 2025
%X 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.
%K Hexokinase: genetics
%K Hexokinase: metabolism
%K Hexokinase: immunology
%K Humans
%K Animals
%K T-Lymphocytes: immunology
%K T-Lymphocytes: metabolism
%K T-Lymphocytes: transplantation
%K Mice
%K Tumor Microenvironment: immunology
%K Xenograft Model Antitumor Assays
%K Cell Line, Tumor
%K Glycolysis
%K Immunotherapy, Adoptive: methods
%K Neoplasms: immunology
%K Neoplasms: therapy
%K Neoplasms: metabolism
%K Cytokines: metabolism
%K Lymphocyte Activation
%K Female
%K T-cells (Other)
%K TCR (Other)
%K cellular immunotherapy (Other)
%K hexokinase 2 (Other)
%K immunometabolism (Other)
%K Hexokinase (NLM Chemicals)
%K HK2 protein, human (NLM Chemicals)
%K Cytokines (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40181966
%2 pmc:PMC11965122
%R 10.3389/fimmu.2025.1477929
%U https://inrepo02.dkfz.de/record/300244