We review the currently available clinical safety and efficacy data with CSF1/CSF1R-targeting agents and provide a comprehensive overview of ongoing clinical studies. Thus, the role of macrophages in regulating tumorigenesis and the impact of depleting and/or reprogramming TAM as therapeutic approaches for cancer patients may vary greatly depending on organ-specific characteristics of these cells. As our knowledge of macrophage biology expands, it becomes apparent that the complex phenotypic and functional properties of macrophages are heavily influenced by a continuum of survival, differentiation, recruitment, and polarization signals within their specific tissue environment.

In the malignant disease setting, data on the clinical activity of immunotherapy combinations with CSF1/CSF1R-targeting agents are pending. The specificity of these agents and their potent blocking activity has been substantiated by impressive response rates in diffuse-type tenosynovial giant cell tumors, a benign connective tissue disorder driven by CSF1 in an autocrine fashion. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents.

In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells.

Poster boys 2017 review