Chemokine Receptor Antibodies

The chemokine receptor family comprises seven-transmembrane receptors that regulate cell migration and positioning in response to chemokine gradients. Conventional chemokine receptors belong to the CC (CCR), CXC (CXCR), XC (XCR), and CX₃C (CX₃CR) subfamilies, named for the arrangement of conserved cysteine residues in their ligands. Most conventional receptors couple predominantly to Gi/o and activate pathways that control cell polarity, adhesion, and directional migration. They are expressed on distinct subsets of leukocytes and, depending on the receptor, on endothelial, stromal, and tumor cells. Their functions include immune surveillance, inflammatory cell recruitment, and the retention of hematopoietic stem cells in bone marrow. Agonist-induced phosphorylation and β-arrestin recruitment can promote receptor desensitization and internalization, with subsequent recycling or degradation depending on the receptor and ligand. Atypical chemokine receptors (ACKRs) generally lack conventional G protein signaling and shape chemokine gradients through ligand scavenging or transport. Clinically approved agents include the CCR5 antagonist maraviroc for CCR5-tropic HIV-1 infection and the CXCR4 antagonist plerixafor for hematopoietic stem cell mobilization. The CXCR4 antagonist mavorixafor is approved in the United States for WHIM syndrome, and the CCR4-directed antibody mogamulizumab is used to treat certain cutaneous T-cell lymphomas.