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- W4313374678 abstract "Abstract Tyrosine kinase inhibitors have been actively investigated as potential therapies for various cancers including blood tumors. However, as T cell activation can also be mediated by various tyrosine kinases, relevant inhibitors are also now being considered as pharmacological modulators of CAR-T cells; an example being dasatinib, which has been found to modulate CAR-T activity through Lck inhibition. T cell activation and subsequent differentiation are tightly associated with cellular metabolism, with T cells showing dynamic changes in two primary metabolic activities of glycolysis and mitochondrial respiration throughout the T cell life cycle. This metabolic response begins with an immediate early increase in glycolytic activity which has been shown to be an essential and signature response to activation. In this study, this fundamental biological process is exploited using the Agilent Seahorse XF technology, illustrating how activation can be measured in real-time in response to anti-CD3/CD28 activator injection, and further, how this parameter can be used to conveniently determine the modulatory effect of kinase inhibitors on T cell activation. Consistent with previous observations that kinase inhibitors can suppress naive T cell activation in vitro, here a similar kinase dependency in re-activation of resting (pre-activated) T cells was observed. Several kinase inhibitors also were able to downregulate the glycolytic rate elevated when applied post-activation. Taken together these data suggest that real-time metabolic analysis is a valuable tool in the characterization of putative T cell modulators, including tyrosine kinase inhibitors, and has the potential to inform the design of specific CAR-T modulators." @default.
- W4313374678 created "2023-01-06" @default.
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- W4313374678 date "2020-05-01" @default.
- W4313374678 modified "2023-09-27" @default.
- W4313374678 title "Metabolic analysis of tyrosine-kinase inhibitor effect on T cell activation" @default.
- W4313374678 doi "https://doi.org/10.4049/jimmunol.204.supp.73.2" @default.
- W4313374678 hasPublicationYear "2020" @default.
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