Nicola Ferrari, Director of Translational Science Lead for Respiratory and Immunology at AstraZeneca, shared a post on LinkedIn:
“Co-infusion of CD19-targeting and BCMA-targeting CAR-T cells for treatment-refractory SLE
In a phase 1 trial, the co-infusion of CD19-targeting and BCMA-targeting CAR-T cells in adults with treatment-refractory lupus was safe and had promising efficacy, with most patients achieving remission after 3 months.
- The authors report results from a cohort of patients (14 female, one male) in an ongoing phase 1 dose-escalation trial of co-infused autologous anti-CD19 and anti-BCMA chimeric antigen receptor (CAR) T cells after fludarabine/cyclophosphamide lymphodepletion.
- Over a median 712-day follow-up (range, 613-1,134), no DLTs occurred. Grade 1 cytokine release syndrome developed in 86.7% of patients, with no neurotoxicity or treatment-related deaths.
- Symptoms related to SLE continuously improved in all 15 patients, with SLEDAI-2K scores reaching zero in 12 of 15 patients and a score of 4 in three patients at 3 months after administration.
- Multiomic analyses confirmed elimination of autoreactive CD19 BCMA clones, reconstitution of naive IgM/IgD B cells, and durable downregulation of interferon-stimulated and BAFF-dependent signatures, indicating improved immune homeostasis.
- Longitudinal monitoring of three patients for 1 year demonstrated sustained eradication of pathogenic clones, suggesting potential cure.
This study supports the further development of this treatment approach for patients with rSLE. Larger, controlled trials with extended follow-up are warranted to clarify long-term efficacy, safety, and mechanistic underpinnings and to optimize CAR-T cell therapy for broader use in SLE.”
Title: Co-infusion of CD19-targeting and BCMA-targeting CAR-T cells for treatment-refractory systemic lupus erythematosus: a phase 1 trial
Authors: Jingjing Feng, Dawei Huo, Ruimin Hong, Xuexiao Jin, Heng Cao, Mi Shao, Rui Wen, Qiqi Zhang, Mingming Zhang, Shan Fu, Dongrui Wang, Huijun Xu, Guoqing Wei, Jiazhen Cui, Simao Huang, Dawei Cui, Alex Hongsheng Chang, Zhihong Liu, Linrong Lu, Jin Lin, Yongxian Hu, He Huang
Read the Full Article in nature medicine.
More posts featuring Nicola Ferrari on OncoDaily.