Figure 5.

mTOR and JAK inhibitors do not inhibit CD19-TCB antitumor efficacy in vivo. Humanized NSG mice were engrafted with a lymphoma PDX (5 million cells, s.c.). When tumors reached 200 mm³, mice were randomized in groups of eight or seven based on their tumor size. They were treated with vehicle (intravenously), 5 mg/kg sirolimus (p.o.), 30 mg/kg ruxolitinib (p.o.), 20 mg/kg dasatinib (p.o.), two times 1 mg/kg, 0.5 mg/kg, four times 0.25 mg/kg dexamethasone (p.o.) alone or in combination with 0.5 mg/kg CD19-TCB (intravenously), 0.5 mg/kg CD19-TCB (intravenously) as a monotherapy. (A–D) Tumor growth curves were plotted from tumor volumes measured using a Caliper, mean of n=6–8 mice+SD with *p≤0.05, **p≤0.01, ***p≤0.001 by one-way ANOVA (Kruskal-Wallis test). (E) Trends of CD3 counts in the tumors at experiment termination. Tumor sections were immunohistochemically stained with anti-CD3 (brown) and nuclei were counterstained with hematoxylin. CD3⁺ T cells were quantified in the different sections with the Visiopharm software. (F) The levels of IL-2, IFN-γ, IL-6 and TNF-α in the serum of the mice collected 6 hours post first infusion with CD19-TCB. The statistical differences to CD19-TCB treatment are summarized in the table. Mean of n=6–8 mice+SD with *p≤0.05, **p≤0.01, ***p≤0.001 by one-way ANOVA (Kruskal-Wallis test). ANOVA, analysis of variance; IFN, interferon; IL, interleukin; PDX, patient-derived xenograft; s.c., subcutaneously; p.o., orally; TCB, T cell bispecific antibody; TNF, tumor necrosis factor.