Novel combination therapy for rheumatoid arthritis: efficacy of anti-CD3 antibody enhanced by p38 inhibitor (Work packages 1-4)

类风湿性关节炎的新型联合疗法：p38 抑制剂增强抗 CD3 抗体的疗效（工作包 1-4）

• 批准号: MR/P50208X/1
• 负责人: Michael Ehrenstein
• 金额: $ 19.24万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP50208X%2F1
• 关键词: Novel; combination; therapy; rheumatoid; arthritis

Anti-CD3 therapy has the potential to have long-lasting efficacy for patients with type 1 diabetes following a brief course of therapy, which if translated to the treatment of RA could reduce or even remove the need for frequent biologic therapy with all the associated financial and healthcare benefits. However, its pathway into the clinic has been hampered by variable responses and side effects, the latter caused by inflammatory cytokine release. This application outlines a proof-of-mechanism study to determine whether the side effects of the anti-CD3 therapeutic antibody Otelixizumab (OTX) could be mitigated and clinical response enhanced, by co-administration of an inhibitor of the inflammatory nodal kinase p38.

抗cd3治疗对于1型糖尿病患者在短期治疗后具有持久疗效的潜力，如果转化为RA的治疗，可以减少甚至消除对频繁生物治疗的需求，并带来所有相关的经济和医疗效益。然而，它进入临床的途径一直受到不同反应和副作用的阻碍，后者是由炎症细胞因子释放引起的。本申请概述了一项机制验证研究，以确定抗cd3治疗性抗体Otelixizumab （OTX）的副作用是否可以通过联合给药炎症结节激酶p38抑制剂来减轻和增强临床反应。