The colony-stimulating factor 1 receptor (CSF1R) is a tyrosine kinase receptor primarily expressed on myeloid cells, including monocytes, macrophages, and microglia. It binds to its ligands, CSF1 and interleukin-34 (IL-34), regulating the survival, proliferation, and differentiation of these cells. Dysregulation of CSF1R signaling is implicated in diseases like cancer, inflammatory disorders, and neurodegenerative conditions, where excessive macrophage activation or accumulation drives pathology.
CSF1R-targeting antibodies are therapeutic or research tools designed to block CSF1R-ligand interactions or receptor activation. In oncology, they aim to deplete tumor-associated macrophages (TAMs) that promote immunosuppression and tumor progression. Preclinical studies show that CSF1R inhibition can enhance anti-tumor immunity and synergize with checkpoint inhibitors. In inflammatory diseases (e.g., rheumatoid arthritis), these antibodies may suppress pathogenic macrophage-mediated tissue damage. Neurodegenerative applications focus on modulating microglia activity in conditions like Alzheimer’s disease.
Several monoclonal antibodies (e.g., emactuzumab, cabiralizumab) have entered clinical trials, though challenges like compensatory signaling, variable efficacy, and on-target toxicity (e.g., liver enzyme elevation) remain. Research continues to optimize dosing, explore combination therapies, and identify biomarkers for patient stratification. CSF1R antibodies represent a promising strategy to modulate myeloid cell dynamics in diverse disease contexts.