Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, is primarily secreted by activated T cells, monocytes, macrophages, and neutrophils. It signals through two receptor complexes: the type II OSM receptor (OSMR/gp130) and the leukemia inhibitory factor receptor (LIFR/gp130), activating downstream pathways like JAK-STAT, MAPK, and PI3K-AKT. OSM plays dual roles in physiological and pathological processes, regulating inflammation, tissue remodeling, cell proliferation, and differentiation. However, dysregulated OSM expression is implicated in chronic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease), fibrosis, and cancer progression, making it a therapeutic target.
OSM-neutralizing antibodies are designed to block OSM-receptor interactions, thereby inhibiting pro-inflammatory signaling and pathological tissue responses. Preclinical studies highlight their potential in attenuating inflammation, reducing extracellular matrix deposition in fibrotic diseases, and suppressing tumor growth or metastasis in certain cancers. For instance, anti-OSM antibodies have shown efficacy in mouse models of colitis and arthritis by dampening immune cell infiltration and cytokine production. In oncology, OSM's context-dependent role—promoting epithelial-mesenchymal transition in some cancers while exerting tumor-suppressive effects in others—underscores the need for biomarker-guided therapies.
Current research focuses on optimizing antibody specificity and delivery to minimize off-target effects, given OSM's overlapping signaling with LIF and IL-6. Early-phase clinical trials are evaluating safety in autoimmune and fibrotic diseases. Challenges include navigating OSM's pleiotropic effects and ensuring long-term therapeutic benefits without disrupting its homeostatic functions in tissue repair. Despite these hurdles, OSM antibodies represent a promising strategy for precision immunotherapy.