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ARTICLE | Preclinical News

NCI team details method to improve T cell therapies

March 29, 2019 7:52 PM UTC

A team led by NCI's Nicholas Restifo showed raising potassium levels or adding a citrate derivative when manufacturing adoptive T cell therapies could improve antitumor efficacy.

Reported in a Science paper, the researchers showed that growing T cells under conditions of high extracellular potassium concentrations led to a reduction in acetyl-coenzyme A (acetyl CoA) levels in the nucleus and cytoplasm of the T cells, and an increase in mitochondrial levels. Those changes helped the T cells maintain characteristics associated with stem cells -- persistence, self-renewal and multipotency -- and have been linked with successful treatment outcomes with checkpoint inhibitors and adoptive T cell therapies. Growing the T cells in the presence of 2-hydroxycitrate, which inhibits generation of cytoplasmic acetyl CoA, led to similar results...