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Background <p>Autoimmune disorders(AIDs) such as systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), immune thrombocytopenic purpura (ITP), and ANCA-associated vasculitis (AAV) are driven by pathogenic autoantibodies from memory B-cells, plasma cells (PCs) and long-lived plasma cells (LLPCs). Since B-cell–only therapies do not eliminate autoantibodies from PCs/LLPCs, we evaluated our novel BCMA-CD19 compound chimeric antigen receptor T-cell (cCAR) therapy. Building on robust preclinical findings, this study aimed to translate cCAR from bench to bedside for refractory SLE overlap syndrome(OS).</p> Methods <p>In vitro co-culture assays were performed using BCMA + MM.1S, BCMA + RPMI-8226, and CD19 + K562 cells at various effector to targe ratios. cCAR induced 86–95% lysis of BCMA + targets and 98% lysis of CD19 + cells. In vivo, NSG mice engrafted with BCMA + MM.1S or REH cells received cCAR T-cells, achieving &gt; 99% target clearance by day 15 and a significant survival benefit. Clinically, a 53-year-old woman with a 10-year history of refractory SLE OS and Class III lupus nephritis was preconditioned with cyclophosphamide and infused with 3 × 10⁶ cCAR cells/kg.</p> Results <p>Preclinical studies confirmed potent in vitro and in vivo cytotoxicity. Clinically, B-cells became undetectable by day 3 post-infusion, and the patient experienced a transient, manageable grade 1 cytokine release syndrome(CRS). Autoantibodies, complement, and urinary protein normalized; the SLE Disease Activity Index 2000(SLEDAI-2K) score dropped from 8 to 0, with durable, medication-free complete remission maintained for over 1.5 years.</p> Conclusion <p>cCAR therapy effectively eliminates pathogenic cell populations, representing a promising translational strategy for treating refractory SLE and related AIDs.</p>

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Validation of BCMA-CD19 Compound CAR-T Therapy in SLE Overlap Syndrome: Over 1.5-Year Follow-Up

  • 期刊论文

  • 发表日期：

    2025年6月23日

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  • Min Wang,
  • Vincent M. DeStefano,
  • Ling Ding,
  • Ming Hong,
  • Ronghao Zeng,
  • Masayuki Wada,
  • Kevin Pinz,
  • Jennifer E. Chow,
  • Nicole Hershkowitz,
  • Mingxia Wang,
  • Chanjuan Zou,
  • Yu Ma,
  • Shanzhi He,
  • Yupo Ma,
  • Weijia Wang

摘要

Background

Autoimmune disorders(AIDs) such as systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), immune thrombocytopenic purpura (ITP), and ANCA-associated vasculitis (AAV) are driven by pathogenic autoantibodies from memory B-cells, plasma cells (PCs) and long-lived plasma cells (LLPCs). Since B-cell–only therapies do not eliminate autoantibodies from PCs/LLPCs, we evaluated our novel BCMA-CD19 compound chimeric antigen receptor T-cell (cCAR) therapy. Building on robust preclinical findings, this study aimed to translate cCAR from bench to bedside for refractory SLE overlap syndrome(OS).

Methods

In vitro co-culture assays were performed using BCMA + MM.1S, BCMA + RPMI-8226, and CD19 + K562 cells at various effector to targe ratios. cCAR induced 86–95% lysis of BCMA + targets and 98% lysis of CD19 + cells. In vivo, NSG mice engrafted with BCMA + MM.1S or REH cells received cCAR T-cells, achieving > 99% target clearance by day 15 and a significant survival benefit. Clinically, a 53-year-old woman with a 10-year history of refractory SLE OS and Class III lupus nephritis was preconditioned with cyclophosphamide and infused with 3 × 10⁶ cCAR cells/kg.

Results

Preclinical studies confirmed potent in vitro and in vivo cytotoxicity. Clinically, B-cells became undetectable by day 3 post-infusion, and the patient experienced a transient, manageable grade 1 cytokine release syndrome(CRS). Autoantibodies, complement, and urinary protein normalized; the SLE Disease Activity Index 2000(SLEDAI-2K) score dropped from 8 to 0, with durable, medication-free complete remission maintained for over 1.5 years.

Conclusion

cCAR therapy effectively eliminates pathogenic cell populations, representing a promising translational strategy for treating refractory SLE and related AIDs.