Background/Purpose: SLE is characterized by B cell activation, autoantibody production and autoreactivity. Recently, CAR-T therapy has emerged as a promising strategy to deplete autoreactive B cells and induce sustained remission. CTA313 is a CD19/BCMA dual-targeted “off-the-shelf” universal CAR-T product with T cell receptor and human leukocyte antigen class knockout, as well as ANSWERTM inhibitory molecule overexpression to resist host immune rejection – leading to increased expansion and persistence in the context of standard dose lymphodepletion. The study aims to evaluate the safety, efficacy and cellular kinetics of CTA313 in patients with active SLE.

Methods: Patients received a single administration of CTA313 treatment at 2 dose levels (DLs): DL1 as 3×106 CAR+ T cells/kg, DL2 as 6×106 CAR+ T cells/kg following lymphodepletion with cyclophosphamide (300 mg/m2, day -5 to -3) and fludarabine (30 mg/m2, day -5 to -3). Cellular kinetics are measured by quantitative PCR and flow cytometry; pharmacodynamics assessments include quantification of B cells, complement (C3/C4), and autoantibodies. Clinical activity assessments include disease activity scores (SLEDAI-2K), Physician’s Global Assessment (PGA) and renal outcome measures.

Results: As of April 30, 2025, seven patients with active SLE received CTA313 at two doses, DL1 (n=3), DL2 (n=4). Six (86%) patients were female, median age 43 (22-50) years, median disease duration 6 (1.3-13.0) years, and 2 patients had lupus nephritis. All patients had been previously treated with steroids and immunosuppressive drugs, including hydroxychloroquine (n=7), tacrolimus (n=7), mycophenolate mofetil (n=4), cyclosporine A (n=2), thalidomide (n=2), and methotrexate (n=1), and one patient received belimumab. To date, treatment has been well tolerated with only Grade 1 cytokine release syndrome (CRS) observed in four of seven patients; no neurotoxicity, GvHD or infections were reported. Hypogammaglobulinemia, which did not require intravenous immunoglobulin treatment, was a common adverse event.With 5 patients reaching initial disease assessment, preliminary efficacy indicated reductions in SLEDAI-2K and PGA. All 5 patients achieved SRI-4 response, and 4 of 5 patients achieved Lupus Low Disease Activity State (LLDAS). Importantly, three patients discontinued all immunosuppressive agents, including glucocorticoids, achieving drug-free remission. Autoantibodies levels declined, accompanied with increasing level of C3. Meanwhile, 24-hour proteinuria significantly decreased in 2 patients with lupus nephritis. PK analysis revealed median peak expansion (Cmax) of 286,265 copies/ug DNA by qPCR at Day 7-10. Complete B cell depletion was observed by Day 4-7 post-infusion. To date, B cell recovery was observed in 3 patients, with median B cell aplasia of 42 days. In patients who achieved anti-dsDNA antibody eradication, the antibody remained undetectable despite B cell reconstitution.

Conclusion: Preliminary data from this trial suggest favorable safety, CAR T cell expansion, B cell depletion and promising clinical activity of CTA313 in active SLE. Ongoing follow up and dose escalation in additional patients will provide insights into long term safety and efficacy.

Figure 1. SLEDAI-2K score and PGA

Figure 2. Anti-dsDNA antibodies and complement C3

Figure 3. B cells

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/preliminary-safety-efficacy-and-cellular-kinetics-of-cta313-a-cd19-bcma-dual-targeted-universal-car-t-therapy-for-active-systemic-lupus-erythematosus/