Enhancing Metabolic Fitness of T -Cells to Treat Central Nervous System Tumors
This T cell-based immunotherapy aims to enhance anti-tumor immune response by addressing metabolic restrictions within tumor microenvironments. T cells play a crucial role in targeting immune responses and adaptive immunity. However, their ability to respond to cancer cells is often limited by tumor evasion tactics. Tumors impose severe glucose restrictions, creating intense competition for this critical nutrient, which is necessary for effective T cell function. Currently, adoptive T-cell transfer therapies have emerged as viable therapeutics but are hindered by the immunosuppressive nature of tumor environments. T cell activity and survival depend on metabolic reprogramming and upon activation there is an increased need for glucose. In the tumor microenvironment, glucose is limited, and T cell responsiveness is limited, resulting in immune evasion and cancer progression. Every year, an estimated 1.9 million people are diagnosed with cancer in the United States, many of whom could benefit from improved immune-based treatments. As the demand for innovative cancer treatments grows, the immunotherapy market continues to expand rapidly. In 2023, the global cancer immunotherapy market was valued at $119 billion and is projected to reach $198 billion by 2030.
Researchers at the University of Florida have developed glucose transporter overexpressing T-cells to enhance the metabolic fitness of T cells. This therapy addresses the glucose restrictions in the tumor microenvironment, where tumors consume most of the glucose and release high levels of lactate, suppressing T-cell function. Leveraging insights into tumor and T-cell metabolism, an additional therapeutic strategy reprograms T cells to interpret lactate as a positive signal, boosting glycolysis, activation, and tumor-targeting capabilities.
Application
Boosts T cell glucose uptake to improve survival and tumor-targeting, offering potential breakthroughs for brain tumor patients, especially those with high-grade gliomas
Advantages
- Improves survival and function of T cells by overexpressing glucose transporters, circumventing the restrictive glucose environments tumors create on glucose
- Uses ex vivo expansion of tumor-specific lymphocytes, ensuring a robust, tumor-focused immune response upon transfer back into the patient
- Uses autologous lymphocytes, reducing the risk of rejection and enhancing the safety of the therapy
Technology
T-cells play an important role in targeting immune response and adaptive immunity. However, their ability to respond to cancer cells is limited by tactics employed by tumors to evade the immune system, particularly glucose restriction. Available therapies focus on targeting tumors through external interventions like surgery, and chemotherapy. However, these can carry serious side effects and are less suitable for metastatic or widespread cancers. Traditional immune therapy is quite promising, using the body’s natural defenses to fight cancer, is limited by the complex immunosuppressive tumor microenvironment. Researchers at the University of Florida have developed a glucose transporter overexpressing T-cells to bypass the immune evasion that the tumor microenvironment promotes. This therapy modifies T-cells to increase glucose uptake, enabling them to survive and function in the nutrient-limited tumor microenvironment. Additionally, it reprograms T-cells to interpret lactate, a byproduct of tumor metabolism that usually suppresses immune function as a signal to enhance T-cell glycolysis, activation, and tumor targeting. These approaches improve the metabolic fitness of T-cells, helping them overcome glucose competition and immunosuppression in tumors.
Brochure
