Innate Lymphoid Cell Engagers (ILCEs): Targeting Innate Lymphoid Cells through a Bispecific Engager for the Resolution of Chronic Inflammation

Objective

Chronic inflammatory diseases, such as rheumatoid arthritis (RA) and spondyloarthropathies (SpA) represent a persistent healthcare challenge, requiring life-long management because of treatments with limited long-term efficacy. The key to a breakthrough may lie in the strategic engagement of Innate Lymphoid Cells (ILCs), whose potential in resolving inflammation and reprogramming tissue memory emerges from the recent ERC-funded research by Rauber et al. (2024). The study published in Nature Immunology elucidates the physiological function of ILCs to control inflammation. Building on this, we propose an innovative ILC engager (ILCE), aiming to harness natural pathways of resolution of inflammation and to offer a significant improvement over anti-cytokine therapies. Our approach bypasses generalized immunosuppression and thereby reduces the risk of infection by maintaining the body's acute inflammatory response. The development of an ILCE holds the promise to gain a new class of precise and efficacious therapeutics for chronic inflammatory diseases, revolutionizing patient outcomes by tailoring treatments to the nuanced pathophysiology of inflammation.