Background/Purpose: Systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are autoimmune conditions characterized by B cell activation, autoreactivity, and autoantibody production. CAR-T therapy has emerged as a promising strategy to deplete autoreactive B cells and induce sustained remission. This study evaluates the safety, efficacy and cellular kinetics of CTA311, a CD19 targeted “off-the-shelf” universal CAR-T product, in patients with active autoimmune disease.

Methods: Patients received a single administration of CTA311 treatment at 4 dose levels (DLs): DL1 as 0.2 ×106 CAR+T cells/kg, DL2 as 1×106 CAR+T cells/kg, DL3 as 3×106 CAR+T cells/kg, DL4 as 6×106 CAR+T cells/kg following lymphodepletion with cyclophosphamide (300mg/m2/day×3) and fludarabine (30 mg/m2/day×3). Clinical activity assessments include disease activity scores (SLEDAI-2K) and Physician’s Global Assessment (PGA).

Results: As of April 30, 2025, eleven patients (10 SLE and 1 AAV) received CTA311 at various doses, DL1 (n=3), DL2 (n=2), DL3 (n=3), and DL4 (n=3). Ten (91%) patients were female, median age 31 (range 25-55) years, median disease duration 6 (range 1-23) years. All had previously been treated with steroids and immunosuppressants, and 6 patients received biological agents (3 telitacicept, 1 belimumab, and 2 both). Treatment was well tolerated; CRS events occurred in 82% (n=9), all low grade (G) (7 G1 and 2 G2). No neurotoxicity was reported. Transient lymphodepletion-related cytopenia ( < 28 days) were observed in all patients. Three patients experienced infections deemed to be treatment related (1 pt with pneumonia (G3) and CMV reactivation (G1), 1 pt with fungal infection (G2), and 1 pt with infection NOS (G1)), which all completely resolved within 2 months. Preliminary efficacy indicated reductions in SLEDAI-2K and PGA accompanied by improvements in autoantibodies, C3, and proteinuria. All 10 patients achieved a Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response, and Lupus Low Disease Activity State (LLDAS) was attained in 4 patients. Two patients achieved DORIS remission. The AAV patient’s BVAS score improved from 8 at baseline to 0 at M3 and M4. However, patient resurgence of mild arthritis) M6. All patients discontinued immunosuppressants and decreased/stopped steroid (≤10 mg/d). PK analysis revealed median peak expansion (Cmax) of 93,679 (range 84-1,091,116) copies/ug DNA approximately 7-11 days post-infusion. Complete B cell depletion was observed by Day 4 post-infusion and persisted for about 1-3 months. In pts that achieved dsDNA Ab eradication, the Ab remained undetected up to 12 months, and ongoing, despite B-cell recovery.

Conclusion: Preliminary data suggest favorable safety, CAR-T cell expansion, B cell depletion and promising efficacy of CTA311 in B cell-mediated autoimmune diseases. Ongoing follow up and enrollment in additional indications will provide insights into long-term safety and efficacy.

Figure 1. SLEDAI-2K score

Figure 2. CAR-T cells

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/preliminary-safety-efficacy-and-cellular-kinetics-of-cta311-a-cd19-targeted-universal-car-t-therapy-for-active-autoimmune-diseases/