Multiple CAR-T cell therapies targeting autoimmune diseases demonstrated promising clinical outcomes at EULAR 2025, with researchers presenting data showing sustained remissions across several severe rheumatic conditions. The presentations highlighted the potential for B cell-depleting therapies to fundamentally reset aberrant immune responses in patients with treatment-refractory autoimmune diseases.
Sustained Responses in Systemic Sclerosis
Wolfgang Merkt presented compelling long-term data on a patient with rapidly progressive systemic sclerosis (SSc) and interstitial lung disease who received third-generation CD19-CAR-T cells in 2022. The patient maintained CAR-T cell persistence and B cell depletion over 24 months, achieving stable serological remission and major disease improvement. Notably, fibrotic lesions and areas of activated fibroblasts continued to regress in the second year of treatment following prolonged deep B cell depletion.
Dinesh Khanna described initial findings from the RESET-SScTM Phase 1/2 trial evaluating resecabtagene autoleucel, a fully human, autologous 4-1BB anti-CD19-CAR T cell therapy designed to deeply and transiently deplete CD19 positive cells. Three-month follow-up data from three patients demonstrated early immunomodulatory-free clinical responses and deep B cell depletion in tissue, as evidenced by lymph node biopsy.
Expanding Applications Across Autoimmune Conditions
The RESET-MyositisTM trial explored resecabtagene autoleucel in three patients with idiopathic inflammatory myopathy. Raj Tummala reported that the approach was well-tolerated with no dose-limiting toxicity, cytokine-release syndrome (CRS), or immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with at least one-month follow-up demonstrated early immunomodulatory-free clinical responses with a favorable safety profile.
In systemic lupus erythematosus (SLE), multiple CAR-T approaches showed efficacy. The RESET-SLETM Phase 1/2 trial evaluated resecabtagene autoleucel in six patients with non-renal SLE or lupus nephritis. Saira Sheikh reported that over 1-9 months of follow-up, clinical improvement was observed in all patients, with multiple patients achieving DORIS remission or complete renal response while remaining free of immunosuppressants.
Eric Morand showcased 12-month data from an open-label Phase 1/2 study of rapcabtagene autoleucel in 21 patients with severe refractory SLE. The findings demonstrated marked improvement in disease activity, effective B cell depletion with recovery of naive B cell phenotype, and a safety profile consistent with CD19-CAR-T therapy in autoimmune disease.
Novel Manufacturing and Targeting Approaches
Vaneet Sandhu's team developed a CAR-T cell product derived from a clonal master cell bank engineered from an induced pluripotent stem cell line, enabling mass production of off-the-shelf CAR-T cells for broad patient access. Preliminary data from the first three patients in a multi-center Phase 1 study indicated a favorable safety profile, effective B cell depletion with reconstitution of more naive B cells, and promising initial efficacy.
Qiong Fu presented data on GC012F (AZD0120), a CD19/BCMA dual-targeting CAR-T evaluated in 10 patients with SLE. At month 9, 70% of patients had stopped glucocorticoids and 40% had discontinued hydroxychloroquine. All patients achieved normalization of complement levels after CAR-T infusion, and 60% achieved persistent serological conversion of ANA, ENA, and anti-dsDNA antibodies. No ICANS or grade 3 or higher CRS were reported.
First Applications in Rheumatoid Arthritis and Vasculitis
Zhu Chen reported findings from three patients with rheumatoid arthritis refractory to multiple conventional and biologic agents. All patients achieved DAS28-CRP remission at 12 weeks post-infusion. Rheumatoid factor disappeared in all three patients, and anti-cyclic citrullinated peptide disappeared in two patients and significantly decreased in the third. The study demonstrated the feasibility of fourth-generation CAR-T cell treatment in difficult-to-treat rheumatoid arthritis.
Ioanna Minopoulou shared results for CAR-T therapy in ANCA-associated vasculitis through a case study of a 52-year-old man with severe refractory disease. After infusion, CAR-T cells expanded rapidly, peaking on day 14 and declining over six weeks. The patient developed grade 1 CRS managed with tocilizumab and grade 3 neutropenia resolved with filgrastim. Symptoms resolved and granulomas stabilized, with the patient remaining symptom-free without immunosuppressive treatment despite return of CD19+ B cells at seven months.
Assessment Tools and Future Directions
Christina Bergmann and colleagues analyzed trajectories of disease activity indexes in 12 patients before and after CD19-CAR-T treatment using the revised European Scleroderma Trials and Research Group Activity Index (EUSTAR-AI) and American College of Rheumatology Composite Response Index (ACR CRISS). Results showed that the majority of patients improved on both measures, with median time to achieve EUSTAR <2.5 (inactive disease) and ACR CRISS ≥0.6 (good response) being 211 and 80.5 days, respectively.
The collective findings suggest the potential for CAR-T cell therapy and other B cell-depleting therapies to reset the immune system in multiple rheumatic and musculoskeletal diseases, allowing patients to achieve meaningful clinical responses without ongoing immunosuppressive therapies.
