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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02964-1

摘要内容如下：

双特异性T细胞结合分子（BITE）通过结合T细胞杀死B细胞。BITES对急性淋巴细胞白血病非常有效。在这里，我们使用CD19xCD3 BITE Blinatumomab治疗了6例多药耐药类风湿性关节炎（RA）患者。低剂量的Blinatumomab导致B细胞耗竭和伴随的T细胞减少，证明了它们的接合功能。治疗是安全的，在首次输注期间体温和急性期蛋白短暂升高，但没有临床相关细胞因子释放综合征的迹象。Blinatumomab使所有患者的RA临床疾病活动度迅速下降，改善了超声和Fapi-PET-CT中的滑膜炎，并降低了自身抗体。B细胞的高维流式细胞术分析记录了免疫重置，激活的记忆性B细胞耗竭，被非类别转换的IgD阳性幼稚B细胞取代。总之，这些数据表明了咬伤治疗类风湿性关节炎的可行性和潜力。这种方法值得进一步探索其他B细胞介导的自身免疫性疾病。

英文原文如下：

Abstracts

Bispecific T cell engagers (BiTEs) kill B cells by engaging T cells. BiTEs are highly effective in acute lymphoblastic leukemia. Here we treated six patients with multidrug-resistant rheumatoid arthritis (RA) with the CD19xCD3 BiTE blinatumomab under compassionate use. Low doses of blinatumomab led to B cell depletion and concomitant decrease of T cells, documenting their engager function. Treatment was safe, with brief increase in body temperature and acute phase proteins during first infusion but no signs of clinically relevant cytokine-release syndrome. Blinatumomab led to a rapid decline in RA clinical disease activity in all patients, improved synovitis in ultrasound and FAPI-PET-CT and reduced autoantibodies. High-dimensional flow cytometry analysis of B cells documented an immune reset with depletion of activated memory B cells, which were replaced by nonclass-switched IgD-positive naïve B cells. Together, these data suggest the feasibility and potential for BiTEs to treat RA. This approach warrants further exploration on other B-cell-mediated autoimmune diseases.

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