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Updated: Jun 22, 2025
06:10
Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
Published on: May 9, 2025
182
Genetically engineering glycolysis in T cells increases their antitumor function.
Raphaëlle Toledano Zur1, Orna Atar2, Tilda Barliya1
1Bar-Ilan University, Ramat Gan, Israel.
Journal for Immunotherapy of Cancer
|July 4, 2024
Summary
Metabolically engineered T cells enhance cancer immunotherapy. By boosting glucose metabolism, these modified cells better compete with tumors, leading to improved antitumor responses and therapeutic potential.
Area of Science:
- Immunology
- Metabolic Engineering
- Cancer Biology
Background:
- T cells are crucial for antitumor responses but are often hindered by nutrient scarcity in the tumor microenvironment.
- Cancer cells outcompete T cells for essential metabolites like glucose, limiting immune function.
Purpose of the Study:
- To enhance T-cell antitumor function by improving their glycolytic capacity to compete with tumor cells.
- To engineer T cells for increased metabolic fitness within the tumor microenvironment.
Main Methods:
- Engineered human T cells to express phosphofructokinase (a glycolysis enzyme) and Glucose transporter 3.
- Co-expressed these metabolic enhancements with tumor-specific chimeric antigen or T-cell receptors.
Main Results:
- Engineered T cells showed increased cytokine secretion and activation markers.
- Demonstrated superior glycolytic capacity and improved in vivo therapeutic potential in a human tumor xenograft model.
Conclusions:
- T-cell metabolic engineering can significantly enhance cellular immunotherapy efficacy.
- This approach offers a promising strategy to overcome tumor microenvironment limitations for cancer treatment.
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