I-BET762 acts synergistically with copanlisib in vivo to inhibit ATL growth in xenograft mice-bearing ATL tumors. (A) Therapeutic effects of I-BET762 and copanlisib combination in xenograft mice-bearing ATL43Tβ (-) cell line. Ten million cells were subcutaneously implanted into NSG mice. The therapy was started when average tumor volumes reached approximately 100 mm³, which was 10 days after tumor inoculation. I-BET762 was given orally at a dose of 15 mg/kg, and copanlisib was administered via intraperitoneal injection at a dose of 9 mg/kg 5 days on and 2 days off for 28 days. The vehicle group received 15% solutol dissolved in water. (B) Average tumor volumes during the therapeutic time course were measured twice weekly until the tumor volume reached 2000 mm³. (C) Serum levels of human sIL-2Rα were measured on day 28 after treatment with a human CD25/IL-2Rα ELISA assay. (D) Kaplan-Meier survival curves illustrate the survival of mice that received single therapy or in combination. Data were pooled from 2 independent experiments and expressed as a mean ± SEM (n = 9 to 12). One-way ANOVA and log-rank (Mantel-Cox) test were performed to determine statistical differences. ****P < .0001.