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IL-1β is a highly potent cytokine that drives the acute phase inflammatory response and has an essential role in the innate immune response. As in many receptor-ligand systems, IL-1β signaling is complex, with multiple ligands interacting with membrane-bound and soluble forms of several receptors. The complexity of receptor-ligand system presents a challenge for the selection of therapeutic anti-IL-1β antibodies. The optimal antibody would selectively attenuate systemic high-level IL-1β signaling to lower, beneficial levels while allowing very high local concentrations of IL-1β to initiate protective inflammatory responses (in response to infection, for instance).
XOMA 052, a recombinant monoclonal antibody with long circulating half-life, high affinity, and high specificity for IL-1β, that simultaneously reduces the affinity of IL-1β for IL-1RI (K′RL >KRL) while leaving affinity for IL-1RII and the soluble inhibitory receptors largely unaffected by antibody binding. XOMA 052 is a potent inhibitor of IL-1β activity both in vitro and in vivo.