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.

双特异性 T 细胞接合剂 (BiTE) 通过接合 T 细胞来杀死 B 细胞。 BiTE 对急性淋巴细胞白血病非常有效。在这里，我们在同情使用下使用 CD19xCD3 BiTE blinatumomab 治疗了 6 名多重耐药类风湿性关节炎 (RA) 患者。低剂量的 blinatumomab 导致 B 细胞耗竭，同时 T 细胞减少，记录了它们的接合功能。治疗是安全的，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。博纳吐单抗导致所有患者的 RA 临床疾病活动迅速下降，超声和 FAPI-PET-CT 中滑膜炎得到改善，自身抗体减少。 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 B 细胞被耗尽，并被非类别转换的 IgD 阳性初始 B 细胞取代。总之，这些数据表明 BiTE 治疗 RA 的可行性和潜力。这种方法值得对其他 B 细胞介导的自身免疫性疾病进行进一步探索。