Under compassionate use, chimeric antigen receptor (CAR) T cells have elicited durable remissions in patients with refractory idiopathic inflammatory myopathies (IIMs). Here, we report on the safety, efficacy, and correlative data of the first subject with the immune-mediated necrotizing myopathy (IMNM) subtype of IIM who received a fully human, 4-1BBz anti-CD19-CAR T cell therapy (CABA-201) in the RESET-Myositis phase I/II trial (NCT06154252). CABA-201 was well-tolerated following infusion. Notably, no evidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was observed. Creatine kinase levels decreased, and muscular strength improved post-infusion. Peripheral B cells were depleted rapidly following infusion, and the subject achieved peripheral B cell aplasia by day 15 post-infusion. Peripheral B cells returned at 2 months post-infusion and were almost entirely transitional. Autoantibodies to SRP-9, SRP-72, SRP-54, and Ro-52, decreased relative to baseline, whereas antibodies associated with pathogens and vaccinations remained stable. The infusion product consisted of predominantly CD4+ effector memory T cells and exhibited in vitro cytolytic activity. Post-infusion, CABA-201 expansion peaked at day 15 and was preceded by a serum IFN-γ peak on day 8 with peaks in serum IL-12p40 and IP-10 on day 15. These data detail the safety, efficacy, and pharmacodynamics of CABA-201 in the first IMNM subject.

中文翻译：

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CD19 CAR T 疗法在 RESET-肌炎 I/II 期试验中接受治疗的免疫介导坏死性肌病受试者的案例研究


在同情使用下，嵌合抗原受体 （CAR） T 细胞在难治性特发性炎症性肌病 （IIM） 患者中引起了持久的缓解。在这里，我们报告了第一个患有免疫介导的坏死性肌病 （IMNM） IIM 亚型的受试者的安全性、有效性和相关数据，该受试者在 RESET-肌炎 I/II 期试验 （NCT06154252） 中接受了全人 4-1BBz 抗 CD19-CAR T 细胞疗法 （CABA-201）。CABA-201 输注后耐受性良好。值得注意的是，未观察到细胞因子释放综合征或免疫效应细胞相关神经毒性综合征的证据。输注后肌酸激酶水平降低，肌肉力量改善。外周 B 细胞在输注后迅速耗尽，受试者在输注后第 15 天出现外周 B 细胞再生障碍。外周 B 细胞在输注后 2 个月返回，几乎完全是过渡性的。SRP-9、SRP-72、SRP-54 和 Ro-52 的自身抗体相对于基线有所下降，而与病原体和疫苗接种相关的抗体保持稳定。输注产物主要由 CD4 + 效应记忆 T 细胞组成，并表现出 体外溶细胞活性。输注后，CABA-201 扩增在第 15 天达到峰值，之前在第 8 天出现血清 IFN-γ 峰值，在第 15 天出现血清 IL-12p40 和 IP-10 峰值。这些数据详细说明了 CABA-201 在第一个 IMNM 受试者中的安全性、有效性和药效学。