Objectives This study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients with systemic lupus erythematosus (SLE) with lupus nephritis (LN). Methods This is a single-arm open-label multicentre phase 1 study of BCMA and CD19-directed cCAR in patients suffering from SLE/LN with autoantibodies produced by B cells and plasma/long-lived plasma cells. In this clinical trial, we sequentially assigned biopsy-confirmed (classes III–V) LN patients to receive 3×10 6 cCAR cells/kg postcessation of all SLE medications and conditioning. The primary endpoint of safety and toxicity was assessed. Complete immune reset was indicated by B cell receptor (BCR) deep sequencing and flow cytometry analysis. Patient 11 (P11) had insufficient lymphocyte counts and was underdosed as compassionate use. Results P1 and P2 achieved symptom and medication-free remission (MFR) from SLE and complete remission from lymphoma. P3–P13 (excluding P11) received an initial dose of 3×10 6 cCAR cells /kg and were negative for all autoantibodies, including those derived from long-lived plasma cells, 3 months post-cCAR and the complement returned to normal levels. These patients achieved symptom and MFR with post-cCAR follow-up to 46 months. Complete recovery of B cells was seen in 2–6 months post-cCAR. Mean SLE Disease Activity Index 2000 reduced from 10.6 (baseline) to 2.7 (3 months), and renal function significantly improved in 10 LN patients ≤90 days post-cCAR. cCAR T therapy was well tolerant with mild cytokine-release syndrome. Conclusions Data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.

Weijia Wang

Shanzhi He

Wenli Zhang

Hongyu Zhang

Vincent M DeStefano

Masayuki Wada

Kevin Pinz

Greg Deener

Darshi Shah

Nabil Hagag

Min Wang

Ming Hong

Ronghao Zeng

Ting Lan

Yu Ma

Fugui Li

Yingwen Liang

Zhencong Guo

Chanjuan Zou

Mingxia Wang

Ling Ding

Yupo Ma

Yong Yuan

Annals of the Rheumatic Diseases

风湿病年鉴 (ARD) 是一份国际同行评审期刊，致力于促进最高标准的科学交流和教育。它涵盖了风湿病学的所有方面，包括肌肉骨骼疾病、关节炎疾病和结缔组织疾病的谱系。 ARD 发表基础、临床和转化科学研究。鼓励简明的科学交流，并以同行评审的国际会议论文集为特色。教育论文包括最先进的评论、“如何”文章和教育案例，重点关注临床实践中面临的问题。该杂志于 1939 年首次出版，拥有权威的全球编辑委员会和不断增长的国际读者群。

The Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal dedicated to promoting the highest standards of scientific communication and education. It covers all aspects of rheumatology, including musculoskeletal disorders, arthritic diseases, and connective tissue diseases. ARD publishes basic, clinical, and translational scientific research, encouraging concise scientific communication and featuring peer-reviewed conference proceedings. Educational papers include cutting-edge reviews, 'how-to' articles, and educational cases, focusing on issues faced in clinical practice. Since its first publication in 1939, the journal has maintained a prestigious global editorial board and a growing international readership.

《Annals of the Rheumatic Diseases》（风湿病年鉴，ARD）是一份国际同行评审的学术期刊，旨在促进高标准的科学交流与教育。期刊涵盖风湿病学的各个方面，包括肌肉骨骼疾病、关节炎和结缔组织疾病等。ARD发表基础研究、临床研究和转化科学研究，鼓励简洁明了的科学交流，并定期刊登国际会议的同行评审论文。教育类论文包括前沿评论、实用指南和教育案例，重点关注临床实践中遇到的问题。该杂志自1939年创刊以来，拥有权威的全球编辑委员会和不断扩大的国际读者群。

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial

Data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.

BCMA-CD19 复合CAR T细胞治疗系统性红斑狼疮：一项1期开放标签临床试验

Category	Quartile
医学	1
医学, 风湿病学	1

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info