Modeling the pharmacokinetic-pharmacodynamic relationship of the monoclonal anti-macaque-IL-15 antibody Hu714MuXHu in cynomolgus monkeys.

Hu714MuXHu is a recombinant chimeric murine-human monoclonal antibody directed against interleukin-15 (IL-15), a proinflammatory cytokine associated with memory CD8+ and natural killer (NK) T-cell activation and implicated in the pathogenesis of inflammatory diseases. A pharmacokinetic-pharmacodynamic (PK/PD) model was developed to describe the NK cell count reduction in cynomolgus monkeys after treatment with Hu714MuXHu. Cynomolgus monkeys were dosed with Hu714MuXHu in three studies: as a single dose at 0.

Homeostasis of human NK cells is not IL-15 dependent.

IL-15 is a proinflammatory cytokine that plays an important role in the development and activation of NK cells and is a potential target for inflammatory disease therapy. Studies conducted in IL-15- and IL-15R knockout mice identified IL-15 as an important cytokine for NK cell homeostasis. Consistent with this information derived from genetically modified mice, we demonstrated that neutralizing IL-15 with a mouse anti-mouse IL-15 mAb (M96) depletes C57BL/6 mouse NK cells.