Figure 1.
AMG 701 induced potent T-cell–redirected lysis of MM cell lines and autologous MM patient cells from RRMM. (A-B) MM cell lines sensitive and resistant to current MM therapies were incubated with healthy donor T cells (n = 5) at an E:T ratio of 10 to 1 (10:1) in the presence of AMG 701 for 24 hours, followed by quantitative FC analysis to determine percent lysis of CD138+ MM cells (A) and percentage of apoptotic/dead IMiD-resistant MM cells (B). MM1S(R) and H929(R), resistant to both len and pom, are derived from MM1S and H929, respectively.48 Data represent the means (percent lysis) ± standard deviations (SDs) of 3 to 5 independent experiments using T effector cells from healthy donors (n = 5) (A) and patients (n = 3) (B), each performed in triplicate at each dose. Error bars indicate SDs. Also shown in B (left panel) are representative dot plots of the percentage of apoptotic/dead in CD138+ cells from IMiD-resistant MM cell lines. (C-D) AMG 701 was added into mixtures of patient T effector cells (n = 3) and the same cell number of MM1S target cells (E:T=1:1) for 6 hours, followed by FC analysis to determine the percentage of cells expressing surface CD107a (degranulation) (C) and the percentage of Th1 cytokines (D) in CD4 and CD8 T subsets. (E) BMMCs purified from BM aspirates of RRMM patients (n = 10) were directly incubated with AMG 701 for 24 hours in triplicate at each concentration, followed by FC analysis to measure the percent lysis of CD138+ patient MM cells. All data are shown as means ± SDs. **P < .005; ***P < .001; ****P < .0001.

AMG 701 induced potent T-cell–redirected lysis of MM cell lines and autologous MM patient cells from RRMM. (A-B) MM cell lines sensitive and resistant to current MM therapies were incubated with healthy donor T cells (n = 5) at an E:T ratio of 10 to 1 (10:1) in the presence of AMG 701 for 24 hours, followed by quantitative FC analysis to determine percent lysis of CD138+ MM cells (A) and percentage of apoptotic/dead IMiD-resistant MM cells (B). MM1S(R) and H929(R), resistant to both len and pom, are derived from MM1S and H929, respectively.48  Data represent the means (percent lysis) ± standard deviations (SDs) of 3 to 5 independent experiments using T effector cells from healthy donors (n = 5) (A) and patients (n = 3) (B), each performed in triplicate at each dose. Error bars indicate SDs. Also shown in B (left panel) are representative dot plots of the percentage of apoptotic/dead in CD138+ cells from IMiD-resistant MM cell lines. (C-D) AMG 701 was added into mixtures of patient T effector cells (n = 3) and the same cell number of MM1S target cells (E:T=1:1) for 6 hours, followed by FC analysis to determine the percentage of cells expressing surface CD107a (degranulation) (C) and the percentage of Th1 cytokines (D) in CD4 and CD8 T subsets. (E) BMMCs purified from BM aspirates of RRMM patients (n = 10) were directly incubated with AMG 701 for 24 hours in triplicate at each concentration, followed by FC analysis to measure the percent lysis of CD138+ patient MM cells. All data are shown as means ± SDs. **P < .005; ***P < .001; ****P < .0001.

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