Figure 5.
The 7C6 + romidepsin combination therapy increases MICA/B in vivo and inhibits AML. (A-E) NSG mice were inoculated IV with 2 × 106 NB4 cells, which were then analyzed ∼3 weeks later by flow cytometry for identification of human CD45+ human CD33+ mouse CD45.1− cells in the bloods and femoral bone marrows. (A) A drawing and representative flow cytometry plots illustrating this human AML model. (B-C) In 7C6-treated mice, romidepsin enhances the surface MICA/B levels in NB4 cells (B) from the blood (C) but not bone marrow. On day 23 after NB4 inoculation, a subset of mice was bled via submandibular bleeding to analyze the surface MICA/B levels on NB4 by flow cytometry. Subsequently, the mice were treated with the indicated doses of romidepsin plus 0.2 mg 7C6-hIgG1-DANA on days 23 and 24. On day 25, mice were euthanized via CO2 and the surface MICA/B levels on NB4 cells isolated from the (B) blood, and (C) femoral bone marrows were analyzed by flow cytometry. (D-E) Combination therapy with romidepsin and 7C6. On days 18 and 19 after NB4 inoculation, mice were treated with the indicated doses of romidepsin + 0.2 mg of the indicated antibodies. Analysis of leukemia cells was done 1 week later by flow cytometry. Analyses of NB4 cells in the (D) blood and (E) femoral bone marrow are shown. (B-E) Data are median ± interquartile range and are pooled of 2 independent experiments. *P < .05. **P < .01 (Mann-Whitney tests comparing 2 groups at a time).

The 7C6 + romidepsin combination therapy increases MICA/B in vivo and inhibits AML. (A-E) NSG mice were inoculated IV with 2 × 106 NB4 cells, which were then analyzed ∼3 weeks later by flow cytometry for identification of human CD45+ human CD33+ mouse CD45.1 cells in the bloods and femoral bone marrows. (A) A drawing and representative flow cytometry plots illustrating this human AML model. (B-C) In 7C6-treated mice, romidepsin enhances the surface MICA/B levels in NB4 cells (B) from the blood (C) but not bone marrow. On day 23 after NB4 inoculation, a subset of mice was bled via submandibular bleeding to analyze the surface MICA/B levels on NB4 by flow cytometry. Subsequently, the mice were treated with the indicated doses of romidepsin plus 0.2 mg 7C6-hIgG1-DANA on days 23 and 24. On day 25, mice were euthanized via CO2 and the surface MICA/B levels on NB4 cells isolated from the (B) blood, and (C) femoral bone marrows were analyzed by flow cytometry. (D-E) Combination therapy with romidepsin and 7C6. On days 18 and 19 after NB4 inoculation, mice were treated with the indicated doses of romidepsin + 0.2 mg of the indicated antibodies. Analysis of leukemia cells was done 1 week later by flow cytometry. Analyses of NB4 cells in the (D) blood and (E) femoral bone marrow are shown. (B-E) Data are median ± interquartile range and are pooled of 2 independent experiments. *P < .05. **P < .01 (Mann-Whitney tests comparing 2 groups at a time).

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