Monoclonal Antibodies to Chemokine Receptors

Monoclonal antibodies (MAbs) to chemokine receptors are providing remarkable insight into the roles these receptors play in basal leukocyte trafficking for immune response and surveillance as well as cell specific recruitment to sites of inflammation. This latter role in particular has established chemokine receptors as attractive targets for novel antiinflammatory drug discovery. The large number of chemokines and receptors, the complex nature of their distinct and overlapping binding specificities, and the differential expression of receptors on leukocytes may provide the opportunity to develop therapeutics that selectively target subsets of leukocytes and thus avoid the broad immunosuppressive actions of most currently available antiinflammatory drugs (1 ). The major obstacle in the path to such therapeutics is unlikely to be the discovery and development of potent and selective chemokine receptor antagonists, inasmuch as seven transmembrane spanning G-protein couple receptors have proven to be a most successful class of drug targets (2 ). However, sorting through the various and complex functions mediated by a multitude chemokine receptor-ligand interactions in order to ascertain which receptor(s) is responsible for site specific recruitment of cells during initiation, progression, and maintenance of a particular disease will be a formidable task.