Figure 4.
DAC, but not AZA, potentiates HSPC-NK cell anti-leukemic effect in vivo. (A) Adult NSG mice that were injected with luciferase-expressing THP-1 cells in their femur were treated with HMAs with use of dosages as indicated in the figure (in milligrams per millimeter squared) and monitored for tumor load progression every 3 to 4 days by bioluminescence imaging (BLI). Treatment was applied daily from days 4 to 9 in titration #1, and from days 2 to 8 and days 4 to 8 for AZA and DAC, respectively, in titration #2. AZA was injected subcutaneously and DAC intravenously based on current clinical practices. Data are depicted as mean ± SD including 8 to 10 mice per group. Dotted lines indicate upper detection limit for tumor load monitoring (signal saturation). (B-D) THP-1–bearing mice were treated with HMAs with use of the same dosages as described in titration #2, and with a single infusion of HSPC-NK cells, applied at day 4. Survival of NK cells in vivo was supported by recombinant human IL-15, given subcutaneously every 2 to 3 days. (B) Experimental design. (C) Median tumor load at day 17. (D) Fold increase in tumor load after 2 weeks of treatment with DAC alone or in combination with HSPC-NK cells (calculated as the ratio between day 17 and day 3 signals). Data were analyzed with an unpaired, 2-tailed Student t test. IF, intrafemoral.