Figure 4
Figure 4. BV173R (with T315I mutation) treated with dasatinib 10 mg/kg and imatinib 50 mg/kg IP daily for 21 days with and without biweekly ESKM therapy (6 doses of ESKM). The error bars show the fifth and 95th percentiles. (A) Exponential growth curves, from the start of therapy (day 6). The blue bar shows the duration of TKI therapy and the red lines are doses of ESKM. (B) The susceptibility of cell line BV173, resistant cell line BV173R (with BCR-ABL T315I mutation) to ESKM directed ADCC with human PBMCs, and different E:T ratios. (C) The BLI imaging at the end of ESKM/TKI therapy (day 27). ESKM is superior to imatinib and dasatinib for treatment of resistant Ph+ ALL. (D) The BLI of mice engrafted with BV173R treated with ponatinib 10 mg/kg alone and in combination with ESKM × 25 days (days 6 to 30). The green bar shows the duration of ponatinib therapy and the red lines are doses of ESKM. (E) The BLI image on day 57 of mice treated in panel (D), immediately before organ analysis for tumor location and MRD evaluation. (F) Ponatinib + ESKM mice from panel (D) were dissected and the organs imaged for tumor localization. Mouse 1: No detectable disease on any imaging, possible cure. Mouse 2: Gastrointestinal and BM leukemia detected. Mouse 3: Gastrointestinal, BM, and lung leukemia detected, with an uncertain primary source. Mouse 4: Lymphoid tumor in the stomach, no other tumor detected. Mouse 5: Primary lymphoid tumor in the stomach, BM leukemia detected.

BV173R (with T315I mutation) treated with dasatinib 10 mg/kg and imatinib 50 mg/kg IP daily for 21 days with and without biweekly ESKM therapy (6 doses of ESKM). The error bars show the fifth and 95th percentiles. (A) Exponential growth curves, from the start of therapy (day 6). The blue bar shows the duration of TKI therapy and the red lines are doses of ESKM. (B) The susceptibility of cell line BV173, resistant cell line BV173R (with BCR-ABL T315I mutation) to ESKM directed ADCC with human PBMCs, and different E:T ratios. (C) The BLI imaging at the end of ESKM/TKI therapy (day 27). ESKM is superior to imatinib and dasatinib for treatment of resistant Ph+ ALL. (D) The BLI of mice engrafted with BV173R treated with ponatinib 10 mg/kg alone and in combination with ESKM × 25 days (days 6 to 30). The green bar shows the duration of ponatinib therapy and the red lines are doses of ESKM. (E) The BLI image on day 57 of mice treated in panel (D), immediately before organ analysis for tumor location and MRD evaluation. (F) Ponatinib + ESKM mice from panel (D) were dissected and the organs imaged for tumor localization. Mouse 1: No detectable disease on any imaging, possible cure. Mouse 2: Gastrointestinal and BM leukemia detected. Mouse 3: Gastrointestinal, BM, and lung leukemia detected, with an uncertain primary source. Mouse 4: Lymphoid tumor in the stomach, no other tumor detected. Mouse 5: Primary lymphoid tumor in the stomach, BM leukemia detected.

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