11R-VIVIT slows leukemia progression in CLL xenograft model. MEC1 CLL cell line was injected subcutaneously into Rag2^−/−γc^−/− mice. Mice were challenged with 11R-VIVIT (daily intraperitoneal administration of 10 mg/kg) or with vehicle alone starting from day 10 after tumor injection. (A) In vivo VIVIT administration reduces tumor growth. Tumor growth curves obtained in Rag2^−/−γ_c^−/− mice that received a transplant subcutaneously in the left flank of MEC1 cells (10 × 10⁶ cells). Ten days later, mice bearing MEC1 tumors were randomly assigned to one of the following daily intraperitoneal treatments: saline solution (PBS, n = 7) or 10 mg/kg VIVIT (n = 8). We evaluated tumor size by measuring perpendicular diameters with a caliper. Animals were sacrificed when the tumor volume reached 1000 mm³ or when animals showed clinical signs and symptoms. Measurements were stopped when 75% of originally treated mice were still surviving. Statistical analysis was performed with the Student t test (day 33, day 38 and day 40 PBS vs VIVIT, P < .05). (B) In vivo VIVIT administration improves mice survival. Kaplan-Meier survival plot for Rag2^−/−γ_c^−/− mice challenged subcutaneously in the left flank with MEC1 cells (10 × 10⁶ cells). Ten days later, mice bearing MEC1 tumor were randomly assigned to one of the following daily intraperitoneal treatments: saline solution (PBS, n = 15) or 10 mg/kg VIVIT (n = 14). Animals were sacrificed when the tumor volume reached 1000 mm³ or when animals showed clinical signs and symptoms (median survival of untreated group 46 days, median survival of VIVIT treated group 52.5 days, P = .006). Data are from three independent experiments. (C) In vivo anergy reversal: pERK1/2. pERK1/2 expression on MEC1 cells present in the spleen of animals injected with the cell line. At time of sacrifice, spleens were collected, processed, and stained for CD19 and phoshorylated ERK1/2, as described in the “Materials and methods” section. Statistical analysis was performed by use of the Student t test.