Benralizumab

IL-5 (interleukin-5) is a pro-inflammatory protein that functions as an intermediary cytokine in the TH2 (T helper 2) cells response in asthma and other eosinophilic allergic diseases. IL-5 is produced by TH2 cells and ILC2 (group 2 innate lymphoid cells) cells in response to stimulation by alarmins such as TSLP (thymic stromal lymphopoietin) or IL-33, which initiate the inflammatory cascade. IL-5 functions by promoting eosinophil maturation, activation, and migration into target tissues. It binds to the IL-5 specific cell surface receptor IL-5RA (IL-5 receptor alpha) and further recruits the common beta chain receptor (CSF2RB) to initiate downstream signaling through JAK1/2 (Janus kinase 1/2) and STAT5. Activated eosinophils contribute to airway damage through degranulation, resulting in the release of pro-inflammatory cytokines and enzymatic mediators contributing to local inflammation and tissue damage.IL-5 signaling plays a critical role in allergic and eosinophilic asthma subtypes and has been an active area for drug discovery. Antibodies targeting both IL-5 ligand and IL-5 Receptor (IL-5RA) are FDA (Food and Drug Administration) approved for the treatment of severe eosinophilic asthma and other eosinophilic conditions. These antibodies function by neutralizing IL-5-mediated signaling in eosinophils. Additionally, IL-5RA targeting antibodies and CAR (chimeric antigen receptor) -T cells can induce immune-mediated cytotoxicity of IL-5RA-expressing cells, including eosinophils through ADCC (antibody-dependent cellular cytotoxicity) and CAR-T cell mediated killing respectively.