Evaluating the Functional Capability of Circulating Natural Killer Cells in Human Studies

Abstract Introduction: Interleukin-15 (IL-15) appears to be involved in T cell and natural killer (NK) cell homeostasis and immune-mediated diseases. In a first-in-human study of a monoclonal antibody against IL-15 (TEV-53408), a reduction of circulating NK cells was observed in healthy volunteers. In order to determine if there was also a qualitative effect on NK cells, in-vitro functional assessments were performed on the remaining NK cells. Methods: PBMCs were obtained from 81 healthy participants(administered TEV-53408 or placebo) in a single-dose (SD) and a multiple dose (MD) study. Samples were stimulated with phorbol myristate acetate (PMA)/ionomycin to induce degranulation, stained with an NK cell-extracellular panel and CD107a. After fixation, permeabilization, and intracellular staining for perforin, cells were run through a flow-cytometry assay. Results: The collected data demonstrated a standard CD56 bright:dim ratio at all time points. Perforin load (MFI) and % of CD107a expression with or without stimulation suggest that TEV-53408 had no effect on the degranulation ability of NK cells. Discussion: These assessments provide an effective method to assess the phenotype and functionality of remaining NK cells following anti-IL-15 treatment. The results suggest that treatment with TEV-53408 does not affect the functionality of the remaining NK cells during the studied timeframe, despite the reduction of circulating NK cells.