Clever-1

Class

Anti-Clever-1 monoclonal antibody (macrophage checkpoint inhibitor)

Pathway

Reprograms immunosuppressive (M2) macrophages to an immunostimulatory (M1) state, restoring anti-tumor immunity

Notes

original target text: Clever-1 (Common Lymphatic Endothelial and Vascular Endothelial Receptor-1 / Stabilin-1)

Clever-1, also known as Stabilin-1, is a scavenger receptor expressed on subsets of macrophages, lymphatic endothelium, and some vascular endothelium. In tumors, it marks and helps maintain macrophages in an immunosuppressive state (often called M2-like), which dampens local immune responses and supports tumor growth by promoting tissue remodeling, angiogenesis, and clearance of molecules that would otherwise trigger inflammation. Blocking Clever-1 with a monoclonal antibody aims to reprogram these macrophages toward a pro-inflammatory, immunostimulatory (M1-like) phenotype, thereby restoring the capacity of the immune system to recognize and attack malignant cells. This approach belongs to a broader class of strategies known as macrophage checkpoint inhibition, distinct from T-cell checkpoint inhibitors such as those targeting PD-1 or CTLA-4. Because macrophages are abundant in many solid tumors and can dominate the local immune environment, shifting their polarization state is of particular interest in cancers that are poorly responsive to T-cell-directed immunotherapies. The rationale is that by altering the innate immune compartment, tumors otherwise resistant to checkpoint blockade might become more susceptible to immune-mediated control, either alone or in combination with therapies that engage adaptive immunity.