Point of care anti-CD19 CAR-T for autoimmune diseases

Abstract Introduction: Anti-CD19 CAR-T cell therapy has revolutionized the treatment of B-cell malignancies. Given the central role of B cells in many autoimmune disorders, CAR-T therapy is emerging as a potential strategy in immune-mediated diseases. We report our initial experience using locally produced, point-of-care (POC), anti-CD19 CAR-T cells in patients with severe, treatment-refractory autoimmune conditions. Methods: Twelve patients with B-cell–driven autoimmune diseases were treated with Sheba's POC anti-CD19 CAR-T product (CD28 costimulatory domain; NCT02772198). One patient received 1×10⁶ CAR-T cells/kg; all others received 0.6×10⁶ cells/kg due to safety concerns. The primary endpoint was safety, evaluated by the incidence and severity of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Secondary endpoints included disease-specific clinical response, biomarker reduction, organ function improvement, and CAR-T cell expansion. Results: Between April 18, 2024, and July 31, 2025, twelve patients were treated: 3 with refractory rheumatoid arthritis (RA), 6 with severe systemic sclerosis (SSc), 1 with myasthenia gravis (MG), and currently two patients are on treatment, 1 with anti-MDA5–positive dermatomyositis with rapidly progressive interstitial lung disease (RP-ILD), and 1 with polyarteritis nodosa (PAN). Median age was 43 years (range 25–68); 8 were female. Three SSc patients had prior autologous stem cell transplantation (ASCT). The first RA patient, treated with 1×10⁶ cells/kg, developed grade 4 CRS and grade 3 ICANS, both resolved with standard interventions. All subsequent patients received 0.6×10⁶ cells/kg. At this lower dose, two RA patients developed grade 3 CRS without ICANS; one SSc patient had grade 3 ICANS and grade 2 CRS. The remaining patients experienced only grade 0–2 CRS/ICANS. In a median follow-up of 8 months (range 4-16), all three RA patients demonstrated significant clinical improvement. Two became treatment-free, while one continued low-dose methotrexate and abatacept. All RA patients showed marked decline in anti-CCP titers. Among six patients with SSc, four experienced a decrease in modified Rodnan Skin Score (mRSS), indicating improved skin involvement, and in one patient of lung involvement had mild improvement in pulmonary function. The patient with MG showed significant neurologic recovery, with MG-ADL score decreasing to 2, currently with normal saturation at room air after ongoing myasthenia crises, no ptosis and walking independently. Response evaluation in the dermatomyositis and PAN patients is currently ongoing. CAR-T cell expansion was observed in all cases, with peak expansion levels highest in the RA subgroup. Conclusions:POC anti-CD19 CAR-T therapy appears feasible, safe, and clinically beneficial in a subset of patients with severe autoimmune diseases. Toxicity was manageable and dose-dependent. Higher inflammatory burden may correlate with increased toxicity, underscoring the need for disease-specific risk stratification. These results support further investigation into CAR-T cells-based immune modulation for autoimmune conditions