A CCL2-based fusokine as a novel biopharmaceutical for the treatment of CCR2-driven autoimmune diseases

Abstract

Autoimmune diseases represent one of the most challenging clinical entities with unmet medical needs, so the continued development of novel therapeutics is well justified. Most autoimmune diseases are marked by the infiltration of lymphomyeloid cells in target tissues, leading to inflammation and tissue damage. This process is guided by chemokines that act as signaling bridges amidst a complex network of immune cells. For example, monocytes are believed to be the primary cell type responsible for pathology initiation and tissue damage, while T lymphocytes are thought to orchestrate the process by secreting more cytokines/chemokines to amplify leukocyte homing. Many studies have addressed the molecular basis of monocyte recruitment in different autoimmune diseases, and the conclusions pointed to a major role played by monocyte chemoattractant protein 1 (MCP-1), also known as CC chemokine ligand 2 (CCL2), and its cell-surface receptor, CC chemokine receptor (CCR) 2. These findings suggest that by interfering with CCL2 or its receptor, it is possible to inhibit the progression of CCR2-dependent diseases. Therefore, future therapy design targeting a maladapted immune response could target chemokine receptors starting with the CCL2-CCR2 axis.