Dexamethasone Potentiates Chimeric Antigen Receptor T Cell Persistence and Function by Enhancing IL-7Rα Expression.

Dexamethasone is a glucocorticoid that is a mainstay for the treatment of inflammatory pathologies, including immunotherapy-associated toxicities, yet the specific impact of dex on the activity of chimeric antigen receptor T cells is not fully understood. We assessed whether dex treatment given ex vivo or as an adjuvant in vivo with CAR T cells impacted the phenotype or function of CAR T cells. We demonstrated CAR T cell expansion and function were not inhibited by dex. We confirmed this observation using multiple CAR constructs and tumor models, suggesting that this is a general phenomenon. Moreover, we determined that dex upregulated interleukin-7 receptor α on CAR T cells and increased the expression of genes involved in activation, migration, and persistence when supplemented ex vivo. Direct delivery of dex and IL-7 into tumor-bearing mice resulted in increased persistence of adoptively transferred CAR T cells and complete tumor regression. Overall, our studies provide insight into the use of dex to enhance CAR T cell therapy and represent potential novel strategies for augmenting CAR T cell performance during production as well as following infusion into patients.

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