Impact of galactose-containing media on mitochondrial function and CAR-T cell activity
Gross G, Alkadieri S, Meir A, et al. Improved CAR-T Cell Activity Associated With Increased Mitochondrial Function Primed by Galactose. Leukemia. 2024; (doi: 10.1038/s41375-024-02257-z).
Manufacturing chimeric antigen receptor (CAR) T cells in galactose-based media amplifies their mitochondrial activity, thus enhancing their efficacy, according to research. Working with CD19-28z CAR-T cells from acute lymphoblastic leukemia patients enrolled in an ongoing trial, researchers observed that CAR-T clinical products inducing complete response demonstrated higher levels of mitochondrial function. To target cellular metabolism, which has previously been implicated as a potential pathway for improving CAR-T immunotherapy, the investigators removed glucose as the carbon source in the manufacturing media. The galactose-containing media that replaced it boosted mitochondrial activity and improved efficacy in vitro. During in vivo experiments with Nalm6-injected mice, CAR-T cells primed with galactose had a favorable impact on leukemia-free survival compared with cells produced in the usual glucose-based environment.