Researchers at the University of Pittsburgh have developed an innovative approach to growing T cells in the laboratory, potentially improving the efficacy of cancer immunotherapies. The study, published in Cell Metabolism, demonstrates that T cells cultured with a compound called dichloroacetate (DCA) show enhanced longevity and cancer-fighting abilities in a mouse model of melanoma.
Traditional T cell culture methods use glucose-rich media, which can make cells overly reliant on sugar for energy. Greg Delgoffe, senior author of the paper, explains, "The way we traditionally grow T cells in the lab is horribly inefficient. We make millions of T cells and we infuse them back into a patient, but most of the cells die."
The new method involves supplementing the growth medium with DCA, which alters T cell metabolism to better utilize diverse energy sources found in the bloodstream. First author Andrew Frisch notes, "Cell therapy is a living drug that responds to the environment in the body. But there is a major gap between where we are with these therapies and where we could be because the way we feed these cells in the lab does not prepare them well for surviving in the body."
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In mouse experiments, DCA-grown T cells demonstrated remarkable longevity, with over 5% still detectable in circulation nearly a year after infusion. These cells also showed improved tumor control and survival rates in melanoma models compared to traditionally cultured T cells.
According to Dr. Delgoffe, “If we can properly nourish our T cell soldiers in the lab by convincing them to eat the right kind of food, they are better prepared to respond to signals in the body and live much longer. We might be able to have a soldier on guard forever. Just as after getting the chicken pox vaccine, you are protected for life - you’ll never get chicken pox again. That’s the ultimate goal of cell therapies for cancer.”