Fig. 4: Delayed JAK inhibitor co-treatment improves in vivo TSLPRCART activity against a ruxolitinib-sensitive CRLF2-rearranged Ph-like ALL PDX model.
A Luciferase-transduced IGH::CRLF2/JAK2R683G-mutant ALL121 PDX model cells (1e6) were injected IV in NSG mice. Once engraftment was documented by BLI, cohorts of 5 mice were randomized to IV treatment with saline, 1e6 untransduced T cells (UTD), or lower-dose (1e6) or higher-dose (2.5e6) TSLPRCART. Ruxolitinib (rux) chow ad libitum was administered simultaneously at day 0 (green), day 7 (blue), or day 14 (purple) after T cell treatments and continued for 21 days in each cohort until days 21, 28, or 35, respectively. Leukemia burden was measured weekly by BLI. B Human CD3+/CD45+ T cells were quantified weekly by flow cytometry analysis of peripheral blood of mice treated with lower-dose (left panel) or higher-dose (right panel) TSLPRCART. C IFN-γ was measured by ELISA in plasma prepared from weekly peripheral venous blood from mice treated with lower-dose (left panel) or higher-dose (right panel) TSLPRCART. Time-sequenced ruxolitinib co-administration at day 14 (at initial peak of detected CAR T cell expansion) improved long-term leukemia clearance and PDX model ‘remission’ in both lower-dose and higher-dose TSLPRCART cohorts. Statistical analyses were performed for (B) and (C) with one-way ANOVA and Tukey post-test for multiple comparisons for surviving cohorts at day 56. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
