Figure 2.
Preclinical efficacy of daratumumab in CD38-expressing MTCN-bearing mice in 2 different xenograft models. (A) CD38 expression in HuT-78 depicted as histogram of CD38 compared with isotype control-stained cells. (B) CD38 expression in luciferase-GFP–transduced T-PLL cells from patients depicted as histogram of CD38 compared with isotype control-stained cells. (C) Schematic diagram showing experimental design: HuT-78 or primary T-PLL cells from patients were transduced with the lentivirus expressing firefly luciferase-GFP, sorted to >99% purity, and transplanted into Rag−/−γc−/− mice with 2 or 4 million cells, respectively. Mice with PDXs were evaluated for leukemia cell engraftment on an IVIS imager (Perkins-Elmer). After confirming the engraftment of leukemia cells in vivo (1 week for HuT-78 and 3 weeks for primary T-PLL), cohorts of mice were randomly assigned to treatment with vehicle or 8 mg/kg daratumumab (Darzalex Faspro formulation with subcutaneous administration) once a week. Mice were imaged weekly using an IVIS imager, starting 1 week after treatment initiation. Figure made with biorender.com. (D) Representative bioluminescence images of HuT-78 mice with PDXs demonstrating leukemia burden in vehicle-treated (red) and daratumumab-treated (black) cohorts at weeks 2, 3, and 4 after treatment initiation. (E) Luciferase bioluminescence intensity was quantified by measuring total flux (photons/s) in mice using the IVIS-100 and Living Image software at each time point (vehicle n = 5, but 2 vehicle mice died before the week-4 imaging time point; daratumumab n = 4; P < .0001). (F) Survival curve of HuT-78 mice with PDXs treated with vehicle (pink) compared with daratumumab (purple; P = .02). (G) Representative bioluminescence images of mice with xenografts derived from patients with T-PLL demonstrating leukemia burden in vehicle and daratumumab-treated cohorts over time. (H) Luciferase bioluminescence presented as total flux (photons/second) over time of mice with xenografts derived from patients with T-PLL treated with daratumumab (n = 5, purple) vs vehicle (n = 4, pink; P < .0001).

Preclinical efficacy of daratumumab in CD38-expressing MTCN-bearing mice in 2 different xenograft models. (A) CD38 expression in HuT-78 depicted as histogram of CD38 compared with isotype control-stained cells. (B) CD38 expression in luciferase-GFP–transduced T-PLL cells from patients depicted as histogram of CD38 compared with isotype control-stained cells. (C) Schematic diagram showing experimental design: HuT-78 or primary T-PLL cells from patients were transduced with the lentivirus expressing firefly luciferase-GFP, sorted to >99% purity, and transplanted into Rag−/−γc−/− mice with 2 or 4 million cells, respectively. Mice with PDXs were evaluated for leukemia cell engraftment on an IVIS imager (Perkins-Elmer). After confirming the engraftment of leukemia cells in vivo (1 week for HuT-78 and 3 weeks for primary T-PLL), cohorts of mice were randomly assigned to treatment with vehicle or 8 mg/kg daratumumab (Darzalex Faspro formulation with subcutaneous administration) once a week. Mice were imaged weekly using an IVIS imager, starting 1 week after treatment initiation. Figure made with biorender.com. (D) Representative bioluminescence images of HuT-78 mice with PDXs demonstrating leukemia burden in vehicle-treated (red) and daratumumab-treated (black) cohorts at weeks 2, 3, and 4 after treatment initiation. (E) Luciferase bioluminescence intensity was quantified by measuring total flux (photons/s) in mice using the IVIS-100 and Living Image software at each time point (vehicle n = 5, but 2 vehicle mice died before the week-4 imaging time point; daratumumab n = 4; P < .0001). (F) Survival curve of HuT-78 mice with PDXs treated with vehicle (pink) compared with daratumumab (purple; P = .02). (G) Representative bioluminescence images of mice with xenografts derived from patients with T-PLL demonstrating leukemia burden in vehicle and daratumumab-treated cohorts over time. (H) Luciferase bioluminescence presented as total flux (photons/second) over time of mice with xenografts derived from patients with T-PLL treated with daratumumab (n = 5, purple) vs vehicle (n = 4, pink; P < .0001).

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