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

Area of Science:

• Immunology
• Cell Therapy
• Autoimmune Diseases

Background:

• Autoimmune disorders (AIDs) like SLE are driven by pathogenic autoantibodies produced by B-cells and plasma cells.
• Current B-cell therapies are insufficient as they do not eliminate autoantibodies from long-lived plasma cells (LLPCs).
• Novel BCMA-CD19 compound chimeric antigen receptor T-cell (cCAR) therapy is being evaluated for refractory AIDs.

Purpose of the Study:

• To translate the novel cCAR therapy from preclinical research to clinical application.
• To evaluate the efficacy and safety of cCAR therapy in patients with refractory SLE overlap syndrome (OS).

Main Methods:

• In vitro co-culture assays assessed cCAR cell cytotoxicity against BCMA+ and CD19+ cell lines.
• In vivo studies in NSG mice evaluated cCAR T-cell efficacy in clearing tumor cells.
• A clinical trial administered cCAR T-cells to a patient with refractory SLE OS and lupus nephritis.

Main Results:

• Preclinical studies demonstrated potent in vitro and in vivo cytotoxicity of cCAR therapy.
• In the clinical trial, B-cells became undetectable post-infusion, and the patient achieved complete remission for over 1.5 years.
• The patient experienced a manageable cytokine release syndrome (CRS), with normalized autoantibodies, complement, and urinary protein levels.

Conclusions:

• cCAR therapy effectively eliminates pathogenic B-cell and plasma cell populations.
• This therapy represents a promising translational strategy for treating refractory SLE and related autoimmune disorders.
• cCAR therapy shows potential for durable, medication-free remission in severe autoimmune conditions.