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风湿病学中的 T 细胞衔接器

英文原题:T-cell engagers in rheumatology.

查看英文原题

T-cell engagers in rheumatology.

PubMed 2026/04/08(内容时间) Best Pract Res Clin Rheumatol Q1 · IF 7(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

TCEs 在多种难治性自身免疫病中显示出令人鼓舞的早期疗效和可接受的安全性,支持其作为新型治疗策略的潜在作用。仍需更长期的前瞻性研究来确定合适的给药方案、长期安全性和缓解持久性。

研究思路结论见上方概要

T细胞衔接器(TCEs)已改变血液系统恶性肿瘤的治疗。鉴于B细胞在许多自身免疫性疾病发病机制中的核心作用,人们越来越关注将TCEs的应用扩展至风湿病适应证,作为CAR-T 的一种更简单的替代方案。

本叙述性综述总结了TCEs在风湿病学中应用的生物学依据、结构多样性、给药策略以及新兴的临床疗效和安全性。

在回顾的12项研究中,80例患者接受了TCE:33例为SLE,22例为RA,14例为SSc,6例为IIM,2例为PSS,3例为其他适应证。32例患者接受了blinatumomab,16例接受了teclistamab,15例接受了mosunetuzumab,17例接受了另一种TCE。观察到临床改善的早期迹象,包括疾病活动度快速降低、器官特异性表现改善以及血清学生物标志物正常化。尽管如此,许多患者在停止治疗后出现持续或复发的疾病活动。各研究的给药策略存在显著异质性,与肿瘤学中使用的方案相比,累积暴露量更低且治疗持续时间更短,提示潜在的治疗不足可能导致部分患者缓解率较低和疾病复发。46%的患者观察到CRS,其中33%为1级,12%为2级,1%为3级。未报告神经毒性或死亡。

展开英文摘要原文

This narrative review summarizes the biological rationale, structural diversity, dosing strategies, and emerging clinical efficacy and safety regarding the use of TCEs in rheumatology.

Among 12 studies reviewed, 80 patients received a TCE: 33 for SLE, 22 for RA, 14 for SSc, 6 for IIM, 2 for PSS, and 3 for other indications. Thirty-two patients received blinatumomab, 16 teclistamab, 15 mosunetuzumab, and 17 another TCE. Early signs of clinical improvement were observed, including rapid disease activity reduction, improvement in organ-specific manifestations, and normalization of serologic biomarkers. Nonetheless, many patients experienced persistent or recurrent disease activity after treatment discontinuation. There was substantial heterogeneity in dosing strategies across studies, with lower cumulative exposure and shorter treatment duration compared with regimens used in oncology, suggesting potential undertreatment may contribute to lower response rates and disease recurrence in some patients. CRS was observed in 46% of patients, of which 33% were grade 1, 12% were grade 2, and 1% was grade 3. No neurotoxicity or deaths have been reported.

TCEs demonstrated encouraging early efficacy and acceptable safety across several refractory autoimmune diseases, supporting their potential role as a novel therapeutic strategy. Longer prospective studies are needed to define adequate dosing schedules, long-term safety, and durability of response.

论文信息

作者
Nordmann-Gomes A、Khalili L、Wax S、Askanase A
第一作者单位
Columbia University Irving Medical Center, Department of Medicine, Division of Rheumatology, New York, NY, USA.United States
通讯作者单位
Columbia University Irving Medical Center, Department of Medicine, Division of Rheumatology, New York, NY, USA. Electronic address: ada20@cumc.columbia.edu.United States
文献类型
综述
期刊
Best practice & research. Clinical rheumatology2026 Mar
原文标识
PubMed 41951534 · DOI 10.1016/j.berh.2026.102146