Figure 1.
NKTR-255 enhances effector functions of NK cells and increases their responsiveness to MM cell exposure, displaying higher cytotoxicity against MM target cells. PBMCs from healthy donors or patients with MM were treated for 7 days with and without different doses of NKTR-255 or 0.1 μg/mL rhIL-15 (as positive control) and NK cells were subsequently isolated by negative selection using immunomagnetic columns prior to every assay. MM cell lines were labeled with CTV stain and co-incubated with the effector cells in a 4-hour in vitro cytotoxicity assay. The percentage of target cell lysis was assessed by flow cytometry and corrected by background lysis. (A) Dose and T:E ratio-dependency was tested using NK cells from healthy donors as effector cells and KMS12BM MM cell line as target cells. (B) Dose and T:E ratio-dependency was tested using NK cells from a patient with myeloma as effector cells and H929 MM cell line as target cells. (C) NK cells isolated from patients with myeloma were treated with different concentrations of NKTR-255 or rhIL-15 and tested against either primary MM cells isolated from BM aspirate of a patient newly diagnosed with MM or U266 and KMS26 MM cell lines as target cells. The percentage of target cell killing over background (spontaneous lysis of target cells not exposed to NK cells) is shown and results are depicted as mean ± standard deviation (SD). (D-E) CD107a cell surface expression was used as a surrogate for quantifying cellular degranulation of NK cells. CD107a expression on NK cells incubated with different doses of NKTR-255 or rhIL-15 was measured at rest and after target MM cell exposure by flow cytometry. (F and G) IFN-γ (F) and TNFα (G) released by NK cells isolated from patients with MM and incubated with different doses of NKTR-255 or rhIL-15 were measured by ELISA assay before and after the co-incubation with different MM cell lines. Results are expressed as concentration (pg/mL) of cytokine in the culture supernatant and compared for statistical analysis with non-treated NK cells. Data shown represent mean ± SD of triplicates for each condition in the same experiment. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, nsP ≥ .05. BM, bone marrow; MM, multiple myeloma; NK, natural killer; ns, not significant; PBMCs, peripheral blood mononuclear cells; SD, standard deviation; T, target; T:E, target-to-effector.

NKTR-255 enhances effector functions of NK cells and increases their responsiveness to MM cell exposure, displaying higher cytotoxicity against MM target cells. PBMCs from healthy donors or patients with MM were treated for 7 days with and without different doses of NKTR-255 or 0.1 μg/mL rhIL-15 (as positive control) and NK cells were subsequently isolated by negative selection using immunomagnetic columns prior to every assay. MM cell lines were labeled with CTV stain and co-incubated with the effector cells in a 4-hour in vitro cytotoxicity assay. The percentage of target cell lysis was assessed by flow cytometry and corrected by background lysis. (A) Dose and T:E ratio-dependency was tested using NK cells from healthy donors as effector cells and KMS12BM MM cell line as target cells. (B) Dose and T:E ratio-dependency was tested using NK cells from a patient with myeloma as effector cells and H929 MM cell line as target cells. (C) NK cells isolated from patients with myeloma were treated with different concentrations of NKTR-255 or rhIL-15 and tested against either primary MM cells isolated from BM aspirate of a patient newly diagnosed with MM or U266 and KMS26 MM cell lines as target cells. The percentage of target cell killing over background (spontaneous lysis of target cells not exposed to NK cells) is shown and results are depicted as mean ± standard deviation (SD). (D-E) CD107a cell surface expression was used as a surrogate for quantifying cellular degranulation of NK cells. CD107a expression on NK cells incubated with different doses of NKTR-255 or rhIL-15 was measured at rest and after target MM cell exposure by flow cytometry. (F and G) IFN-γ (F) and TNFα (G) released by NK cells isolated from patients with MM and incubated with different doses of NKTR-255 or rhIL-15 were measured by ELISA assay before and after the co-incubation with different MM cell lines. Results are expressed as concentration (pg/mL) of cytokine in the culture supernatant and compared for statistical analysis with non-treated NK cells. Data shown represent mean ± SD of triplicates for each condition in the same experiment. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, nsP ≥ .05. BM, bone marrow; MM, multiple myeloma; NK, natural killer; ns, not significant; PBMCs, peripheral blood mononuclear cells; SD, standard deviation; T, target; T:E, target-to-effector.

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