Wistar scientists enhance cell-based therapy to destroy solid tumors
Source: EurekAlert!, December 2023
PHILADELPHIA—(Dec. 13, 2023)—Wistar researchers successfully tested a simple intervention that could unlock greater anti-tumor power in therapies that use T cells — an approach known as “cell-based therapy,” which uses specially designed T cells to fight cancer. Led by Dr. Hildegund C.J. Ertl — a professor in The Wistar Institute’s Vaccine & Immunotherapy Center — the team has proven an exciting concept: that the common cholesterol drug fenofibrate can boost T cells’ ability to destroy human tumors, as described in their new paper, “Treatment with the PPAR? agonist fenofibrate improves the efficacy of CD8+ T cell therapy for melanoma,” published in Molecular Therapy Oncolytics.
CD8+ T cells work very well in fighting liquid tumors, but for solid tumors like melanoma, the cell-based therapy approach can stall due to the physical structure of the cancer. The T cells infiltrate the tumor, but the cancer adapts and saps the T cells’ energy by hijacking the form of metabolism that the T cells use: glycolysis, which turns sugar into energy. Without energy, the T cells first lose functions and then die, and the cancer continues to grow.
But Dr. Ertl’s team has been able to circumvent this problem by forcing T cells to use a different energy source than glucose. They used fenofibrate because, as a cholesterol-lowering compound, the drug is a PPAR? agonist. When PPAR? is upregulated, cellular metabolism is switched from glycolysis to fatty acid oxidation, or FAO. This mechanism works to improve cholesterol levels in human patients, but for Dr. Ertl’s purposes, the fenofibrate-induced switch to FAO provided T cells with a form of energy that cancer couldn’t exploit — which is how Dr. Ertl proved that fenofibrate has been able to boost the killing power of T cells deployed against cancerous cell lines.