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Abstract: SA-PO0833

B Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy in Refractory Autoimmune Diseases

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Pri Chen, Hadass, Hadassah University Medical Center, Jerusalem, Jerusalem District, Israel
  • Gur, Chamutal, Hadassah University Medical Center, Jerusalem, Jerusalem District, Israel
  • Elias, Shlomo, Hadassah University Medical Center, Jerusalem, Jerusalem District, Israel
  • Stepensky, Polina, Hadassah University Medical Center, Jerusalem, Jerusalem District, Israel
Background

B cells are key drivers of autoimmune diseases, however current B-cell–targeted therapies rarely induce lasting remission. Chimeric antigen receptor (CAR) T-cell therapy is now being explored for autoimmune diseases, and CD19-targeted CAR T cells have shown efficacy in refractory cases. Yet, CD19 is broadly expressed and absent on long-lived plasma cells. In contrast, B-cell maturation antigen (BCMA) is selectively expressed on mature B cells and plasma cells—the primary source of pathogenic autoantibodies. BCMA-directed CAR T-cell therapy has demonstrated efficacy in multiple myeloma (MM). We report the first clinical trial of plasma cell–directed anti-BCMA CAR T-cell therapy in autoimmune disease.

Methods

This Phase I, single-center, dose-escalation trial evaluates HBI0101, an autologous BCMA-directed CAR T-cell product developed at Hadassah Medical Center and validated in MM. Eligible patients include those with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), or idiopathic inflammatory myopathies (IIM) refractory to standard therapies. Patients undergo leukapheresis, and infusion of 450×10^6 CAR-positive T cells; escalation to 800×10^6 is ongoing.

Results

Three patients with severe, treatment-refractory autoimmune disease were treated:
A 29-year-old female with inflammatory myositis (CPK 4138 U/L), wheelchair-bound despite multiple immunosuppressants, regained ambulation by 4 months; CPK fell to 1121 U/L.
A 21-year-old male with diffuse SSc and skin tightening showed improved skin elasticity with confirmed histologic improvement.
A 22-year-old female with class IV+V lupus nephritis had nephrotic-range proteinuria (9 g/24h), hypoalbuminemia (2.1 g/dL), and active inflammatory markers. At 3 months, albumin rose to 4.1 g/dL, proteinuria declined to 4.7 g/24h and inflammatory markers normalized.
Treatment was well tolerated. One patient developed mild cytokine release syndrome; another developed hypogammaglobulinemia, managed with IVIG. No serious infections occurred.

Conclusion

BCMA CAR T-cell therapy induced rapid, substantial improvement in three patients with refractory autoimmune diseases and was well tolerated. These findings underscore the potential of this strategy to redefine treatment in autoimmunity and justify its continued exploration as a targeted, durable, and disease-modifying intervention.

Funding

  • Commercial Support – IMMIX BIOPHARMA

Digital Object Identifier (DOI)