{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:17:55Z","timestamp":1787793475973,"version":"build-2784847793"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["14\/BIAP\/B2959"],"award-info":[{"award-number":["14\/BIAP\/B2959"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Interleukin (IL)25 has been implicated in tissue homeostasis at barrier surfaces and the initiation of type two inflammatory signaling in response to infection and cell injury across multiple organs. We sought to discover and engineer a high affinity neutralizing antibody and evaluate the antibody functional activity in vitro and in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, we generated a novel anti-IL25 antibody (22C7) and investigated the antibody\u2019s therapeutic potential for targeting IL25 in inflammation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A novel anti-IL25 antibody (22C7) was generated with equivalent in vitro affinity and potency against the human and mouse orthologs of the cytokine. This translated into in vivo potency in an IL25-induced air pouch model where 22C7 inhibited the recruitment of monocytes, macrophages, neutrophils and eosinophils. Furthermore, 22C7 significantly reduced ear swelling, acanthosis and disease severity in the Aldara mouse model of psoriasiform skin inflammation. Given the therapeutic potential of IL25 targeting in inflammatory conditions, 22C7 was further engineered to generate a highly developable, fully human antibody while maintaining the affinity and potency of the parental molecule.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The generation of 22C7, an anti-IL25 antibody with efficacy in a preclinical model of skin inflammation, raises the therapeutic potential for 22C7 use in the spectrum of IL25-mediated diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/abt\/tbac022","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T18:39:10Z","timestamp":1664476750000},"page":"258-267","source":"Crossref","is-referenced-by-count":3,"title":["Discovery and multi-parametric optimization of a high-affinity antibody against interleukin-25 with neutralizing activity in a mouse model of skin inflammation"],"prefix":"10.1093","volume":"5","author":[{"given":"Ruth","family":"Bone","sequence":"first","affiliation":[{"name":"Pfizer BioMedicine Design, , Grange Castle Business Park, Clondalkin, Dublin 22 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J","family":"Fennell","sequence":"additional","affiliation":[{"name":"Pfizer BioMedicine Design, , Grange Castle Business Park, Clondalkin, Dublin 22 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Tam","sequence":"additional","affiliation":[{"name":"Pfizer BioMedicine Design, , Cambridge, MA, 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sheldon","sequence":"additional","affiliation":[{"name":"Pfizer Inflammation & Immunology, , Cambridge, MA, 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Nocka","sequence":"additional","affiliation":[{"name":"Pfizer Inflammation & Immunology, , Cambridge, MA, 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreeja","family":"Varghese","sequence":"additional","affiliation":[{"name":"Pfizer BioMedicine Design, , Grange Castle Business Park, Clondalkin, Dublin 22 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chew Shun","family":"Chang","sequence":"additional","affiliation":[{"name":"Pfizer BioMedicine Design, , Cambridge, MA, 02139 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike C","family":"Hawerkamp","sequence":"additional","affiliation":[{"name":"Trinity College Dublin Trinity Biomedical Sciences Institute, School of Medicine, , Dublin 2 , Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife","family":"Yeow","sequence":"additional","affiliation":[{"name":"Trinity College Dublin Trinity Biomedical Sciences Institute, School of Medicine, , Dublin 2 , 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