Plozalizumab (as known as MLN1202) is a humanized monoclonal antibody directed against the human chemokine receptor 2 (CCR2), with potential antiangiogenic, immunomodulating, antimetastatic, and antineoplastic activities. Preclinical studies suggest that CCR2 plays an important role in the trafficking of monocytes and macrophages to sites of inflammation. This drug was developed by Takeda Pharmaceuticals International Co. for the treatment of atherosclerosis, diabetic nephropathies, malignant melanoma. It showed a positive effect in phase II for the treatment of bone metastases.
Monocyte chemoattractant protein-1 (MCP-1; also known as chemokine ligand 2, CCL2) is a chemokine which specifically mediates monocyte chemotaxis and it is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The chemokine receptors mediate agonist dependent calcium mobilization and inhibition of adenylyl cyclase. Human chemokine receptor 2 (CCR2), expressed on the surface of circulating monocytes, and its ligand CCL2 are present in atherosclerotic plaques and may have important roles in endothelial monocyte recruitment and activation. The G-protein coupled receptor CCR2 is expressed on the surface of monocytes and macrophages, stimulates the migration and infiltration of these cell types, and plays an important role in inflammation, angiogenesis, and tumor cell migration and proliferation. Plozalizumab is a highly specific humanized monoclonal antibody that interacts with CCR2 and inhibits MCP-1 binding. When plozalizumab binds to CCR2 and prevents binding of the endothelium-derived CLL2 (monocyte chemoattractant protein-1 or MCP1) to its receptor CCR2, it may result in inhibition of CCR2 activation and so inhibition of angiogenesis, tumor cell migration, and tumor cell proliferation. In addition, this agent may reduce levels of C-reactive protein (CRP).
Fig 1. Mechanism of Action of Plozalizumab