IL-21 expanded NK cells effectively target CLL cells in vitro. (A) NKs and CLL cell line target cells were cocultured at varying effector:target ratios ± 5 μg/mL antibody as noted, and cytotoxicity was measured using a 4-hour calcein release assay. Graphs show mean ± standard deviation of n = 3 NNK, 6 ND-XNK experiments. (B) Comparison of cytotoxic function of ND-XNK vs NNKs against primary CLL cells. Graphs show mean ± standard deviation of n = 6 NNK, 13 ND-XNK experiments. (C) Comparison of CLL target cytotoxicity divided between IGHV mutated vs unmutated (left panel) or with vs without del(17p) (right panel). (D) Comparison of HG3 target cytotoxicity with TP53 WT, R175H, R248Q, or KO. Graphs show mean ± standard deviation of n = 4 experiments. (E) Comparison of CLL target cytotoxicity using 5 μg/mL of rituximab, obinutuzumab, or trastuzumab, compared with no antibody. Graphs show mean ± standard deviation of n = 10 experiments (untreated, rituximab, obinutuzumab) or 5 experiments (trastuzumab). ∗P < .05 by mixed effect modeling.