Characterization and Favorable in Vivo Properties of Heterodimeric Soluble IL-15·IL-15Rα Cytokine Compared to IL-15 Monomer*

• DOI: 10.1074/jbc.m113.461756
• Publication Date: 2013-05-07T00:18:06Z
• Authors: Elena Chertova; Cristina Bergamaschi; Oleg Chertov; Raymond Sowder; Jenifer Bear; James D. Roser; Rachel K. Beach; Jeffrey D. Lifson; Barbara K. Felber; George N. Pavlakis
• Keywords: Interleukin 15; HEK 293 cells

Interleukin-15 (IL-15), a 114-amino acid cytokine related to IL-2, regulates immune homeostasis and the fate of many lymphocyte subsets. We reported that, in blood mice humans, IL-15 is present as heterodimer associated with soluble receptor α (sIL-15Rα). Here, we show efficient production this noncovalently linked but stable clonal human HEK293 cells release processed IL-15·sIL-15Rα medium. Purification sIL-15Rα polypeptides allowed identification proteolytic cleavage site IL-15Rα characterization multiple glycosylation sites. Administration reconstituted from purified subunits resulted sustained plasma levels robust expansion NK T mice, demonstrating pharmacokinetics vivo bioactivity superior single chain IL-15. These identified properties heterodimeric provide strong rationale for evaluation molecule clinical applications.