Dexamethasone potentiates chimeric antigen receptor T cell persistence and function by enhancing IL-7Rα expression.

Dexamethasone (dex) 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 CAR 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 that 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 function during production as well as following infusion into patients.

Evaluation of the antimicrobial efficacy and skin safety of a novel color additive in combination with chlorine disinfectants.

OBJECTIVE: A novel color additive colorizes chlorine disinfectants blue to improve visibility and enhance spray surface coverage, and it fades to colorless to indicate elapsed contact time. We investigated its interactions with 3 chlorine disinfectants to determine if the additive would adversely affect the disinfectants' antimicrobial efficacy or skin safety. METHODS: We tested 0.5% sodium hypochlorite, 0.2% calcium hypochlorite, and 0.5% sodium dichloroisocyanurate (NaDCC) alone versus with color additive. An independent laboratory tested efficacy against Staphylococcus aureus, Pseudomonas aeruginosa, Vibrio cholerae, and human coronavirus 229E. An independent laboratory also tested direct skin irritation. RESULTS: Chlorine disinfectants with and without color additive achieved equal levels of efficacy against the tested pathogens. Against S. aureus, 0.5% sodium hypochlorite with and without color additive met Environmental Protection Agency criteria for disinfection success. Against human coronavirus 229E, 0.5% sodium hypochlorite alone failed disinfection success criteria, whereas 0.5% sodium hypochlorite with color additive achieved full viral inactivation (≥4.50 log10 reduction). Against V. cholerae, 0.2% calcium hypochlorite alone and with color additive achieved 5.99 log10 and >6.03 log10 reductions, respectively. Against S. aureus and P. aeruginosa, 0.5% NaDCC with and without color additive achieved >4.9 log10 and >3.54 log10 reductions, respectively. All 3 chlorine disinfectants with color additive tested as negligible skin irritants. CONCLUSIONS: This color additive can be combined with chlorine disinfectants without adversely affecting antimicrobial efficacy or skin safety.

Novel color additive for chlorine disinfectants corrects deficiencies in spray surface coverage and wet-contact time and checks for correct chlorine concentration.

Bleach sprays suffer from poor surface coverage, dry out before reaching proper contact time, and can be inadvertently over-diluted to ineffective concentrations. Highlight®, a novel color additive for bleach that fades to indicate elapsed contact time, maintained >99.9% surface coverage over full contact time and checked for correct chlorine concentration.