CAR T-Cell Therapy Achieves Long-Term Remission in Autoimmune Diseases Through Complete B-Cell Depletion

Key Insights

• Complete eradication of B cells through CD19-targeted CAR T-cell therapy has enabled sustained drug-free remission in over 40 autoimmune disease patients for up to 4 years.
• The therapy achieves superior B-cell depletion compared to conventional treatments like rituximab, while preserving vaccination antibodies produced by CD19-negative plasma cells.
• When B cells regenerate post-treatment, they display a "reset" profile with predominantly naive cells, suggesting a fundamental reformation of the immune system.

In a groundbreaking development for autoimmune disease treatment, researchers have discovered that the complete elimination of B cells through chimeric antigen receptor (CAR) T-cell therapy leads to sustained, medication-free remission in patients with severe autoimmune conditions.

Dr. Georg Schett from Friedrich-Alexander University of Erlangen-Nuremberg, Germany, revealed that his center has successfully treated more than 40 patients with CD19-targeted CAR T-cell therapy. The treated cohort, including patients with systemic lupus erythematosus and systemic sclerosis, has maintained remission without medication for up to four years.

Mechanism of Action and B-Cell Depletion

The therapy's effectiveness stems from its ability to completely eradicate B cells from patients' bodies. "At one point in time, you probably don't have B cells in the body," Dr. Schett explained during a virtual presentation at Cleveland Clinic. The depletion pattern shows a characteristic "deep, narrow valley" in B-cell counts shortly after treatment initiation.

Notably, long-lived plasma cells in the bone marrow survive the treatment due to their lack of CD19 surface expression, allowing them to maintain essential vaccination antibodies against diseases such as measles, mumps, rubella, tetanus, pneumococcal, and SARS-CoV-2.

Superior Efficacy Compared to Conventional Treatments

The depth of B-cell depletion achieved through CAR T-cell therapy significantly surpasses current treatment options. Lymph node biopsy comparisons revealed complete elimination of B-cell pools with CAR T-cell therapy, while conventional treatments like rituximab left B-cell follicles largely intact. Additionally, the therapy eliminates T-follicular helper cells, which remain unaffected by rituximab treatment.

Immune System Reset and Long-term Effects

Following treatment, the immune system undergoes a significant reset. When B cells eventually return, they exhibit a predominantly naive phenotype with minimal memory B cells. The therapy also maintains a sustained reduction in DN2 cells, which are closely associated with lupus pathogenesis.

Future Prospects

The field of autoimmune CAR T-cell therapy is rapidly expanding, with over 100 studies currently in progress. "I think we will hopefully see exciting news in the next years of how well this therapy works and how safe it is," Dr. Schett noted, highlighting the growing momentum in this therapeutic approach.