Fig. 1: Simultaneous JAK inhibition ameliorates in vivo CAR T cell-induced mortality and suppresses TSLPRCART activity in ruxolitinib-insensitive CRLF2-rearranged Ph-like ALL. | Leukemia

Fig. 1: Simultaneous JAK inhibition ameliorates in vivo CAR T cell-induced mortality and suppresses TSLPRCART activity in ruxolitinib-insensitive CRLF2-rearranged Ph-like ALL.

From: Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia

Fig. 1

A Kaplan-Meier survival analysis of IGH::CRLF2 Ph-like ALL patient-derived xenograft (PDX) mice (JH331 model). Cohorts of 5 mice were randomized and treated intravenously (IV) with 5e6 TSLPRCART or vehicle (saline) control with or without simultaneous exposure to ruxolitinib 2 g/kg rodent chow administered continuously (ad libitum) days 0 through 21 (horizontal green bar). B Human CD45+/CD19+B-ALL cells and (C) human CD45+/CD3+CAR T cells were quantified weekly via flow cytometric analysis of sampled peripheral blood from JH331 mice treated with vehicle, ruxolitinib monotherapy, or lower-dose 1e6 TSLPRCART with or without simultaneous ruxolitinib treatment from days 0 to day 21 (green bar). Lower TSLPRCART numbers are initially detected at early ruxolitinib co-administration timepoints, then normalize in subsequent weeks after ruxolitinib withdrawal. D IFN-γ levels in plasma from JH331 mice treated with 1e6 TSLPRCART in (B) and (C) are lower in mice treated with simultaneous ruxolitinib. Depicted data represent mean ± standard error of the mean (SEM). Statistical analyses were performed with Kaplan-Meier survival analysis with log-rank (Mantel-Cox) for comparison, 2-way ANOVA with Šidák correction, or unpaired t-tests at relevant time points. ns not significant, *p < 0.05, **p < 0.01, ****p < 0.0001.

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