Figure 4.
Figure 4. CD19/CD3-scFv-Fc eliminates CLL cells in patient-derived xenografts with once-weekly dosing. PBMCs from 4 treatment-naïve patients with E:T cell ratios of 1:50 to 1:181 were injected into NSG mice on experimental day 0. Cell engraftment was confirmed on day 3 by flow cytometry. Mice were then treated once weekly with either HER2/CD3-scFv-Fc, CD19/CD3-scFv-Fc, or blinatumomab; an untreated group was left for controls. Two to 5 mice were included for each patient and treatment group (n = 4 patients, n = 51 mice). (A) Representative flow cytometry analysis from the peripheral blood of mice treated with either HER2/CD3-scFv-Fc or CD19/CD3-scFv-Fc at experimental days 3 (top, pretreatment) and 17 (bottom, posttreatment). Gates show CD19+/CD5+ CLL population of live, CD45+, CD8−/CD4− cells. (B) Mean CLL cell count in the peripheral blood over time by treatment group. Arrows denote bsAb injections. (C) CLL cell count in the peripheral blood at experimental day 17. (D) CLL cell count in the spleen at experimental day 17. For panels C and D, each dot represents 1 animal; color code denotes patient source of xenografted cells and correlates with colors in supplemental Table 1. Mean and 95% CI are shown. Asterisks denote significance using unpaired Student t tests, taking into account the random batch effect from xenograft source. *P < .05; **P < .01; ***P < .001; ****P < .0001.

CD19/CD3-scFv-Fc eliminates CLL cells in patient-derived xenografts with once-weekly dosing. PBMCs from 4 treatment-naïve patients with E:T cell ratios of 1:50 to 1:181 were injected into NSG mice on experimental day 0. Cell engraftment was confirmed on day 3 by flow cytometry. Mice were then treated once weekly with either HER2/CD3-scFv-Fc, CD19/CD3-scFv-Fc, or blinatumomab; an untreated group was left for controls. Two to 5 mice were included for each patient and treatment group (n = 4 patients, n = 51 mice). (A) Representative flow cytometry analysis from the peripheral blood of mice treated with either HER2/CD3-scFv-Fc or CD19/CD3-scFv-Fc at experimental days 3 (top, pretreatment) and 17 (bottom, posttreatment). Gates show CD19+/CD5+ CLL population of live, CD45+, CD8/CD4 cells. (B) Mean CLL cell count in the peripheral blood over time by treatment group. Arrows denote bsAb injections. (C) CLL cell count in the peripheral blood at experimental day 17. (D) CLL cell count in the spleen at experimental day 17. For panels C and D, each dot represents 1 animal; color code denotes patient source of xenografted cells and correlates with colors in supplemental Table 1. Mean and 95% CI are shown. Asterisks denote significance using unpaired Student t tests, taking into account the random batch effect from xenograft source. *P < .05; **P < .01; ***P < .001; ****P < .0001.

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