NKTR-255 induces proliferation and activation of BM-derived NK cells, reducing viability of autologous MM cells. (A) Whole BM samples (n = 6) from patients newly diagnosed with MM without prior treatment were incubated for 120 hours with and without 4 increasing doses of NKTR-255. The effect of the compound on the NK (effector) and MM (target) cell populations in whole BM was assessed through an automated flow cytometry platform that allows for absolute cell counting. Based on this data, T:E ratio for each sample was calculated at baseline and it was not modified since the whole BM sample was employed unaltered for this assay. Absolute numbers of NK cells within whole BM samples were measured at baseline and after 120 hours of incubation and results are presented as mean ± standard deviation fold increase in NK cell absolute number in the 6 patients according to concentration level of NKTR-255. (B-C) CD69 and NKG2D expression was measured as a marker of NK cell activation. Percentages of NK cells expressing NKG2D (B) and CD69 (C) over total NK cell population after 120 hours of incubation at different NKTR-255 concentrations are shown as mean and range (minimum to maximum). (D-E) Percentage of live CD138⁺ MM cells in BM samples of each patient (D) was calculated at baseline and after 120 hours of culture with and without different doses of NKTR-255. Mean of CD138+ cell viability compared with untreated is shown (E). ∗∗P < .01, ∗∗∗P < .001, ^nsP ≥ .05. BM, bone marrow; E:T, effector-to-target; ns, not significant; NK, natural killer; MM, multiple myeloma; SD, standard deviation.