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. 2012 Jan 24;20(5):1002–1013. doi: 10.1038/mt.2011.298

Figure 4.

Figure 4

U87mg and Molt-4 cells transduced with the thymidine-activating mutant of deoxyCytidine Kinase (dCK) are sensitive to prodrug-mediated cell killing in vivo in tumor and leukemia models of cancer. (a) Subcutaneous tumors in NOD/SCID mice formed by U87mg cells transduced with dCK.DM.S74E but not control eGFP-transduced cells were efficiently eradicated in vivo by treatment with bromovinyl-deoxyuridine (BVdU) (eGFP, U87mg cells transduced with LV-eGFP; dCK.DM.S74E, U87mg cells transduced with LV-dCK.DM.S74E; +BVdU, treated with 60 mg/kg/day of BVdU for 21 days). (Error bars represent SE of the mean; percentages above the bars represent proportion of mice that had measurable tumors; n = 7–11 for treatment groups and n = 3 for PBS controls; *indicates statistically significant difference, P <0.005). (b,c) Kaplan-Meier survival curves of mice with Molt-4-derived leukemias. Aggressive T cell leukemia was induced in pre-conditioned NOD/SCID animals by intravenous tail vein administration of human Molt-4 cells (dCK.WT, Molt-4 cells transduced with LV-dCK.WT; dCK.DM.S74E, Molt-4 cell transduced with LV-dCK.DM.S74E; PBS, PBS-injected control animals; +LdT, treated with 50 mg/kg/day of L-deoxythymidine (LdT); +BVdU, treated with 50 mg/kg/day of BVdU; dotted line below x-axis underlines the drug treatment window). Survival of mice with established leukemias derived from Molt-4 cells-expressing dCK.DM.S74E was increased with LdT (b) or BVdU (c) treatments (median survival increase of 1 week) administered for 14 days starting day 15 after cell injection (n = 3–10; *indicates statistically significant difference compared to control, P < 0.05). LV, lentiviral vector.