IL-5 receptor alpha (IL5RA) on eosinophils/basophils

Class

anti-IL-5Rα monoclonal antibody (benralizumab, Fasenra; formerly MEDI-563)

Pathway

afucosylated antibody drives antibody-dependent cell-mediated cytotoxicity (ADCC), directly depleting eosinophils rather than just neutralizing IL-5

IL-5 receptor alpha (IL5RA) is the eosinophil- and basophil-restricted subunit of the receptor for interleukin-5 (IL-5), a cytokine that governs the production, maturation, and survival of eosinophils in the bone marrow and their persistence in tissue. In diseases where eosinophils accumulate and contribute to inflammation and tissue damage, such as severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, and certain hypereosinophilic conditions, reducing circulating and tissue eosinophil numbers is a rational therapeutic strategy. Benralizumab is a monoclonal antibody engineered to bind IL5RA directly on the eosinophil surface. Rather than simply blocking IL-5 from engaging its receptor, the antibody has been modified (afucosylated) to bind more tightly to Fc receptors on natural killer cells, triggering antibody-dependent cell-mediated cytotoxicity (ADCC) — the antibody flags the eosinophil for destruction by the immune system's own cytotoxic cells. This approach produces near-complete depletion of eosinophils rather than merely dampening new signaling, distinguishing it from cytokine-neutralizing strategies. Because basophils also express IL5RA, though at lower density, they are affected to a lesser extent as well.