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

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Tornroos H, Hagerstrand H, Lindqvist C

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

Anticancer Res. 2019 Jan;39(1):107-112. doi: 10.21873/anticanres.13085.

PubMed ID
30591446 [ View in PubMed
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Abstract

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 gamma chain (gammac)-dependent cytokines, was measured by traditional tritiated thymidine ([(3)H]-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.

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