578 Lebrikizumab allows interleukin (IL)-13 membrane binding and subsequent internalization through the decoy receptor IL-13 receptor alpha 2 (Rα2)

Abstract

Lebrikizumab (lebri) is a novel, monoclonal antibody that selectively targets IL-13 and prevents formation of the IL-13 receptor alpha 1 (Rα1)/IL-4 receptor alpha (Rα) heterodimer receptor signaling complex. A previous crystal structure report showed that lebri does not interfere with binding of IL-13 to the IL-13 Rα2 decoy receptor. In contrast, other IL-13 antibodies tralokinumab and cendakimab had been reported to inhibit IL-13 binding to both IL-13Rα1 and IL-13Rα2. We wanted to investigate whether lebri binding to IL-13 interfered with IL-13 binding to IL-13Rα2 and the subsequent internalization.