Common lymphatic and endothelial vessel receptor 1 (CLEVER-1) (CLEVER-1)

Common lymphatic and endothelial vessel receptor 1 (CLEVER-1), also known as Stabilin-1, is a large multifunctional scavenger receptor primarily expressed on immunosuppressive M2-type macrophages and lymphatic/sinusoidal endothelial cells (UniProt Q9NY15). It plays a critical role in the silent clearance of unwanted metabolic products, cell adhesion, and lymphocyte trafficking (PubMed: 15123776). In the tumor microenvironment, CLEVER-1 is highly expressed on tumor-associated macrophages (TAMs), where it facilitates immune evasion by suppressing T-cell activation and promoting an anti-inflammatory environment (PubMed: 32814744). Therapeutic targeting of CLEVER-1, notably with monoclonal antibodies like bexmarilimab (FP-1305), aims to switch the phenotype of these macrophages from a pro-tumoral M2 state to a pro-inflammatory M1 state (Faron Pharmaceuticals). This phenotypic switch enhances the recruitment and activation of cytotoxic T-cells, thereby promoting anti-tumor immunity. Beyond oncology, CLEVER-1 is implicated in chronic inflammation and fibrosis due to its role in tissue remodeling and leukocyte migration (PubMed: 21169541).

Other names

Stabilin-1STAB1FEEL-1Fasciclin, EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1MS-1 antigen

Bexmarilimab is a humanized IgG4 monoclonal antibody that acts as an antagonist by binding to the CLEVER-1 receptor on tumor-associated macrophages. This binding blocks the receptor's immunosuppressive signaling and scavenging functions, triggering a conversion of the macrophage phenotype from M2 (pro-tumoral) to M1 (anti-tumoral), which subsequently stimulates a T-cell mediated immune response against the cancer (PubMed: 33106315; Faron Pharmaceuticals).