{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T15:45:08Z","timestamp":1776527108555,"version":"3.51.2"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":338,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK Clinical Research Fellowship","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JGWP Trust"},{"name":"EP Abrahams Trust"},{"name":"Millennium Pharmaceuticals Inc."},{"name":"Tolerx Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>An Fc-mutated chimeric aglycosyl anti-CD3 monoclonal antibody (mAb), otelixizumab, has been used successfully to treat renal transplant rejection and type 1 diabetes, with reduced toxicity compared with traditional anti-CD3 therapies such as OKT3. The aim of this study was to seek preliminary safety data for otelixizumab in rheumatoid arthritis (RA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A small Phase 1 experimental medicine study was performed in six participants with RA. The primary outcome measure was safety, with a focus on first-dose cytokine release reactions and extent of CD3+ lymphopenia. Cytokine release was quantified using ELISA, and lymphocyte subsets by flow cytometry. In vitro whole blood assays were used to interrogate the mechanisms underlying the first-dose cytokine release reaction. Clinical progress following therapy was monitored as an exploratory outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All participants experienced a moderate first-dose cytokine release reaction. There was transient lymphopenia but no T-cell depletion, and a temporary CD8+ T-cell lymphocytosis occurred in all participants. In those who completed therapy, a sustained reduction in CRP following treatment was noted. In an in vitro whole blood assay, designed to mirror in vivo cytokine release, there was a trend for reduced cytokine production in seropositive RA compared with seronegative RA, psoriatic arthritis, or healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>At the dosing regimen used, otelixizumab was associated with an unexpected and significant first-dose reaction in participants with RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/immadv\/ltaf034","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T12:32:36Z","timestamp":1764592356000},"source":"Crossref","is-referenced-by-count":0,"title":["A phase 1 experimental medicine study of anti-CD3 monoclonal antibody in rheumatoid arthritis"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3226-8948","authenticated-orcid":false,"given":"Catherine A","family":"Lawson","sequence":"first","affiliation":[{"name":"Academic Unit of Musculoskeletal Medicine, University of Leeds , Leeds ,","place":["United Kingdom"]},{"name":"Molecular Medicine Unit, Clinical Sciences Building, St. James\u2019s University Hospital , Leeds ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Harry","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bridget","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Academic Unit of Musculoskeletal Medicine, University of Leeds , Leeds ,","place":["United Kingdom"]},{"name":"Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoff","family":"Hale","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman","family":"Waldmann","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6103-7056","authenticated-orcid":false,"given":"John D","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Academic Unit of Musculoskeletal Medicine, University of Leeds , Leeds ,","place":["United Kingdom"]},{"name":"Molecular Medicine Unit, Clinical Sciences Building, St. James\u2019s University Hospital , Leeds ,","place":["United Kingdom"]},{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne ,","place":["United Kingdom"]},{"name":"Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne ,","place":["United Kingdom"]},{"name":"NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals and Newcastle University , Newcastle upon Tyne ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"2026041811114913900_ltaf034-B1","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/nri2134","article-title":"CD3-specific antibodies: a portal to the treatment of autoimmunity","volume":"7","author":"Chatenoud","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"2026041811114913900_ltaf034-B2","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1097\/00007890-198904000-00008","article-title":"Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients","volume":"47","author":"Abramowicz","year":"1989","journal-title":"Transplantation"},{"key":"2026041811114913900_ltaf034-B3","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1056\/NEJM198905253202117","article-title":"Systemic reaction to the anti-T-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-gamma","volume":"320","author":"Chatenoud","year":"1989","journal-title":"N Engl J Med"},{"key":"2026041811114913900_ltaf034-B4","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1097\/00007890-199004000-00009","article-title":"In vivo cell activation following OKT3 administration. 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