An engineered interleukin-11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma.
Bioengineering & translational medicine
2023; 8 (6): e10573
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 to engineer an IL-11 variant that binds with higher affinity to the IL-11 receptor and stimulates enhanced receptor-mediated cell signaling. Introduction of two additional point mutations ablates IL-11 ligand/receptor association with the gp130 coreceptor signaling complex, resulting in a high-affinity receptor antagonist. Unlike wild-type IL-11, this engineered variant potently blocks IL-11-mediated cell signaling and slows tumor growth in a mouse model of lung cancer. Our approach highlights a strategy where native ligands can be engineered and exploited to create potent receptor antagonists.
View details for DOI 10.1002/btm2.10573
View details for PubMedID 38023717
View details for PubMedCentralID PMC10658506