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Lookup NU author(s): Dr Rachel Harry, Dr Bridget Griffiths, Dr Geoff Hale, Professor John IsaacsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Immunology. Introduction: 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). Methods: 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. Results: 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. Conclusions: At the dosing regimen used, otelixizumab was associated with an unexpected and significant first-dose reaction in participants with RA.
Author(s): Lawson CA, Harry R, Griffiths B, Hale G, Waldmann H, Isaacs JD
Publication type: Article
Publication status: Published
Journal: Immunotherapy Advances
Year: 2025
Volume: 5
Issue: 1
Online publication date: 03/12/2025
Acceptance date: 06/11/2025
Date deposited: 06/05/2026
ISSN (electronic): 2732-4303
Publisher: Oxford University Press
URL: https://doi.org/10.1093/immadv/ltaf034
DOI: 10.1093/immadv/ltaf034
Data Access Statement: The data underlying this article are available within the article.
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