An engineered <scp>interleukin</scp>‐1 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma

The cytokine interleukin (IL)-11 has been shown to play a role in promoting fibrosis and cancer, including lung adenocarcinoma, garnering interest as an attractive target for therapeutic intervention. We used combinatorial methods engineer IL-11 variant that binds with higher affinity the receptor stimulates enhanced receptor-mediated cell signaling. Introduction of two additional point mutations ablates ligand/receptor association gp130 coreceptor signaling complex, resulting high-affinity antagonist. Unlike wild-type IL-11, this engineered potently blocks IL-11-mediated slows tumor growth mouse model cancer. Our approach highlights strategy where native ligands can be exploited create potent antagonists.