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Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Hexokinase2-engineered T cells display increased anti-tumor function.

Raphaëlle Toledano Zur¹, Shiran Didi Zurinam¹, Maria Radman¹

¹The Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.

Frontiers in Immunology

|April 4, 2025

Summary

Overexpressing Hexokinase 2 (HK2) in T cells boosts their anti-tumor response by enhancing metabolism. This engineered T cell therapy shows promise for improving cancer treatment in challenging tumor microenvironments.

Keywords:

T-cells TCR cellular immunotherapy hexokinase 2 immunometabolism

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Area of Science:

Immunology
Cancer Biology
Metabolic Engineering

Background:

T cells struggle metabolically in the tumor microenvironment (TME) due to nutrient competition from cancer cells.
This competition impairs T cell anti-tumor activity by reducing critical metabolic functions like glycolysis.
Hexokinase 2 (HK2) is essential for T cell glycolysis and overall functionality.

Purpose of the Study:

To enhance T cell anti-tumor immunity by genetically engineering T cells to overexpress Hexokinase 2 (HK2).
To evaluate the metabolic and therapeutic efficacy of HK2-engineered T cells in vitro and in vivo.

Main Methods:

Primary human T cells were genetically modified to overexpress HK2 and a tumor-specific receptor.
Engineered T cells underwent in vitro testing for metabolic function and activation.
In vivo efficacy was assessed using a human tumor xenograft model.

Main Results:

HK2-engineered T cells demonstrated significantly increased glycolytic capacity.
Enhanced metabolic activity correlated with improved cytokine secretion and activation marker expression.
In vivo studies showed delayed tumor growth and improved survival in the xenograft model.

Conclusions:

Overexpression of HK2 enhances T cell metabolic fitness and functionality within the TME.
This metabolic enhancement translates to improved anti-tumor therapeutic efficacy.
HK2 engineering represents a promising strategy for next-generation immunotherapies targeting T cell metabolism.