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Human NK-92 Cells Function as Target Cells for Human NK Cells - Implications for CAR NK-92 Therapies
Hans Bergman1, Noora Sissala1, Henry HÄgerstrand1
1Cell Biology Unit, Faculty of Natural Sciences and Engineering, Åbo Akademi University, Turku, Finland.
Background/Aim:
Recent studies indicate that chimeric antigen receptor (CAR)-T-cells seem to be superior to CAR modified NK-92 cells. One, at least partial, explanation to this discrepancy has been addressed herein, by having NK-92 cells as target cells in cytotoxicity reactions using peripheral blood mononuclear cells.
Materials And Methods:
A time-resolved fluorometric assay (TDA-labeled NK-92 or K562 as target cells) was used for measuring the cytotoxic activity of blood mononuclear cells (PBMC).
Results:
The cytotoxic capacity of the NK-92 cells was initially demonstrated by their ability to efficiently kill K562 cells. Interestingly, having PBMC as effector cells rendered the very same NK-92 cells sensitive to NK-cell mediated cytolysis. A 1:100 target:effector ratio gave 34.1% lysis compared to 72.2% lysis for K562 cells. Incubating PBMC for longer times (24 up to 48 h) potentiated their NK-activity against NK-92 cells even more, reaching a level close to that obtained with K562 cells.
Conclusion:
This study pinpoints a severe problem that has to be considered in future immune-based cancer therapies with NK-92 as well as CAR-transduced NK-92 cells.
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