In vivo efficacy of XNK cells in CLL xenograft models. (A) Mice were injected IV with 5 × 106 live OSU-CLL or Mec1 cells. 1 × 107 live ND-XNK cells (IV) ± 250 μg obinutuzumab (intraperitoneal) were injected on days 3, 7, 11, and 15. IL-2 (20 000 U) was given by intraperitoneal injection 3 times per week (M/W/F) from day 2 to day 30 and 100 mg/kg venetoclax (Ven) by oral gavage from day 2 to day 30. (B) Mice (n = 5 per group) were injected with OSU-CLL and treated as described in panel A and then followed for survival. (C) Mice (n = 7 per group) were injected with Mec1 and treated as described in panel A, then followed for survival. (D) Mice (n = 7 per group) were injected with Mec1 and treated as described in panel A, then followed for survival. (C-D) Different analyses from the same cohort, presented separately for clarity. (E) Mice from panel D were bled weekly, and NK counts were measured using flow cytometry. HLA-DR expression was quantified on day 9. (F) Mice from panel D (n = 4 to 5 per group) were bled on days 9 and 16, and plasma levels of human IFN-γ, perforin, and granulysin were measured using cytokine bead array. IFN-γ was not consistently detected on day 9. ∗P < .05 using log-rank test (B-D), mixed effect modeling (E), or ANOVA (F); survival curves are labeled if significantly different from untreated.
