Researchers from The Wistar Institute’s Vaccine & Immunotherapy Center have made a significant breakthrough in cell-based therapy for cancer treatment. Led by Dr. Hildegund C.J. Ertl, the team has discovered that a commonly prescribed cholesterol-lowering drug called fenofibrate can enhance the ability of T cells to destroy solid tumors. The findings of their study, titled “Treatment with the PPARα agonist fenofibrate improves the efficacy of CD8+ T cell therapy for melanoma,” have been published in Molecular Therapy Oncolytics.
Cell-based therapy is a promising approach that utilizes specially engineered T cells to combat cancer. While CD8+ T cells have demonstrated success in fighting liquid tumors, they often face challenges when targeting solid tumors like melanoma due to the physical structure of the cancer. Upon infiltrating the tumor, the T cells become depleted of energy as the cancer hijacks their metabolic process, known as glycolysis. Without energy, the T cells lose functionality and eventually die, allowing the cancer to continue growing.
To address this issue, Dr. Ertl’s team explored an alternative energy source for T cells, focusing on fenofibrate, a drug that works as a PPARα agonist to regulate cellular metabolism. Fenofibrate redirects cellular metabolism from glycolysis to fatty acid oxidation (FAO), providing T cells with an energy source that cancer cells cannot exploit. Through their study, the researchers demonstrated that fenofibrate improved the killing power of T cells when targeting cancer cell lines.
Building upon these findings, the team aimed to determine if fenofibrate would have comparable effects when targeting solid tumors. In preclinical models using human solid tumor fragments, the researchers treated T cells with fenofibrate and observed significant improvements. The T cells treated with fenofibrate survived longer and exhibited a higher ability to kill cancer cells compared to the untreated cells.
According to Dr. Hildegund Ertl, treating T cells with fenofibrate triggers a metabolic switch that enhances their cancer-killing capabilities. This intervention shows promise for future anti-tumor therapies, particularly in the treatment of melanoma, the most dangerous form of skin cancer. Any progress made in destroying cancerous cells, even through a simple pre-treatment step like fenofibrate, can have a substantial impact on improving patient outcomes.
These findings open up new possibilities for enhancing the efficacy of cell-based therapies in the treatment of solid tumors. By optimizing T cell metabolism, scientists can potentially overcome the limitations and challenges posed by the tumor microenvironment, paving the way for more effective cancer treatments. Further research and clinical trials will be crucial in exploring the full potential of fenofibrate and similar interventions in combating solid tumors and improving patient survival rates.
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1. Source: Coherent Market Insights, Public sources, Desk research
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