Culturing the Human Natural Killer Cell Line NK-92 in Interleukin-2 and Interleukin-15 - Implications for Clinical Trials.

BACKGROUND/AIM: The human natural killer cell line NK-92 is increasingly being used in adoptive cell immunotherapies, either in vitro or in animal models transduced with different chimeric antigen receptor (CAR) constructs. Herein, NK-92 cells were analyzed with respect to their proliferation and cytotoxicity, in the presence of interleukin-2 (IL-2) and interleukin-15 (IL-15). MATERIALS AND METHODS: A time-resolved fluorometric assay (TDA-labeled K562 target cells) was used for measuring the cytotoxic activity of NK-92 cells treated with IL-2, IL-4, IL-7 and/or IL-15. Their proliferation, in the presence of these common cytokine receptor γ chain (γc)-dependent cytokines, was measured by traditional tritiated thymidine ([3H]-TdR) incorporation. RESULTS: IL-2 and IL-15, but not IL-4 or IL-7, were able to induce a dose-dependent proliferation of NK-92 cells. IL-15 was, depending on the dose and culture time, up to 10 times more potent compared to corresponding concentrations of IL-2, whereas their combination could potentiate the NK-activity almost equally well. No synergistic effects could be noticed with respect to the cytotoxicity and the proliferation of these cells. CONCLUSION: Data presented here indicate that of the common gamma chain receptor-dependent cytokines tested here, IL-15 alone is able to cultivate and trigger NK-92 cells to such an extent so that they can be used for immune-based cancer therapies. Implications with respect to CAR-transduced NK-92 cells are also discussed.

Thymic stromal lymphopoietin augments the cytolytic activity of the human natural killer cell line NK-92.

Culturing the human natural killer cell line NK-92 for 24 h in the presence of thymic stromal lymphopoietin (TSLP) potentiated its cytotoxic capacity against the erythroleukemia cell line K562. Longer incubation times did not augment the NK activity any further. No synergistic effects with respect to either proliferation or cytotoxicity were observed when TSLP was mixed with suboptimal concentrations of IL-2. FACS analysis of the NK-92 cells indicated expression of TSLPR but not the other component of the TSLP receptor complex, namely IL-7Ralpha. Some of the surface molecules known to be involved in NK cell-mediated cytotoxicity were also monitored. None of the receptors analyzed altered their expression to any major extent upon culture in TSLP or IL-2. However, a limited number of NK-92 cells were observed that had a rather low CD94/NKG2A expression, which increased upon stimulation with TSLP or IL-2.