Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor α monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils [1]. Benralizumab can selectively bind to the isoleucine-61 amino acid residue in domain 1 of IL-5Rα, hindering the binding of IL-5 to the related receptor and the subsequent heterodimerization of the α and βc subunits, thereby preventing the activation of the complex signaling pathways associated with IL-5 receptor activation [2]. Benralizumab has been widely used to enhance the activity of natural killer (NK) cells and increase the levels of pro-apoptotic proteins perforin and granzyme B[3].
In vitro, Benralizumab treatment for 22h significantly induced the death of eosinophils or basophils, with EC50 values of 0.9pM and 0.5pM, respectively[4]. Treatment with 5µM Benralizumab for 3 days significantly inhibited the proliferation of HL-60 cells and induced cell cycle arrest, accompanied by a decrease in STAT3 protein levels[5].
In vivo, Benralizumab treatment via intraperitoneal injection at a dose of 10mg/kg every two weeks for 4 weeks significantly reduced IL-33-induced eosinophilic airway inflammation in mice [6].
References:
[1] FitzGerald J M, Bleecker E R, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial[J]. The Lancet, 2016, 388(10056): 2128-2141.
[2] Pelaia C, Calabrese C, Vatrella A, et al. Benralizumab: from the basic mechanism of action to the potential use in the biological therapy of severe eosinophilic asthma[J]. BioMed research international, 2018, 2018(1): 4839230.
[3] Sehmi R, Lim H F, Mukherjee M, et al. Benralizumab attenuates airway eosinophilia in prednisone-dependent asthma[J]. Journal of Allergy and Clinical Immunology, 2018, 141(4): 1529-1532. e8.
[4] Kolbeck R, Kozhich A, Koike M, et al. MEDI-563, a humanized anti–IL-5 receptor α mAb with enhanced antibody-dependent cell-mediated cytotoxicity function[J]. Journal of Allergy and Clinical Immunology, 2010, 125(6): 1344-1353. e2.
[5] Piazzetta G L, Di Agostino S, Lobello N, et al. Preliminary Effects of Benralizumab in an AML Cell Model with Promyelocytic Features Expressing IL-5R: An Exploratory Proof-of-Concept Study[J]. Biomedicines, 2026, 14(3): 652.
[6] Nunomura S, Ito R, Nanri Y, et al. Novel mechanisms by which benralizumab suppresses IgE expression in human B cells in humanized mice[J]. Allergy, 2023, 78(12).