{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:14:52Z","timestamp":1787026492435,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Patients with severe eosinophilic asthma (SEA; characterized by persistent eosinophilia in blood and airway tissues) experience frequent asthma exacerbations with poor clinical outcomes. Interleukin 5 (IL-5) and IL-5 receptor alpha subunit (IL-5\u03b1) play key roles in eosinophilia maintenance, and relevant therapeutic strategies include the development of antibodies (Abs) against IL-5 or IL-5\u03b1 to control eosinophilia. Benralizumab, an anti\u2013IL-5\u03b1 Ab that depletes eosinophils mainly\n                    <jats:italic>via<\/jats:italic>\n                    Ab-dependent cell-mediated cytotoxicity and through blockage of IL-5 function on eosinophils, has been clinically approved for patients with SEA. Here, we report engineering of a new humanized anti\u2013IL-5R\u03b1 Ab with potent biological activity. We first raised murine Abs against human IL-5R\u03b1, humanized a leading murine Ab, and then further engineered the humanized Abs to enhance their affinity for IL-5R\u03b1 using the yeast surface display technology. The finally engineered version of the Ab, 5R65.7, with affinity (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>D<\/jats:sub>\n                    \u2248 4.64 nM) stronger than that of a clinically relevant benralizumab analogue (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>D<\/jats:sub>\n                    \u2248 26.8 nM) showed improved neutralizing activity toward IL-5\u2013dependent cell proliferation in a reporter cell system. Domain level Ab epitope mapping revealed that 5R65.7 recognizes membrane-proximal domain 3 of IL-5R\u03b1, distinct from domain I epitope of the benralizumab analogue. In\n                    <jats:italic>ex vivo<\/jats:italic>\n                    assays with peripheral eosinophils from patients with SEA and healthy donors, 5R65.7 manifested more potent biological activities than the benralizumab analogue did, including inhibition of IL-5\u2013dependent proliferation of eosinophils and induction of eosinophil apoptosis through autologous natural-killer-cell\u2013mediated Ab-dependent cell-mediated cytotoxicity. Our study provides a potent anti\u2013IL-5R\u03b1 Ab, 5R65.7, which is worthy of further testing in preclinical and clinical trials against SEA as a potential alternative to the current therapeutic arsenal.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2020.593748","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T15:42:00Z","timestamp":1610120520000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Engineering of Humanized Antibodies Against Human Interleukin 5 Receptor Alpha Subunit That Cause Potent Antibody-Dependent Cell-Mediated 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