This report summarizes the key findings from presentations on cell-based therapies, including CAR-T and CAR-NK therapies, at the EULAR 2025 Congress. The summaries are based exclusively on the content of the provided abstract book and are organized by disease.
Systemic Lupus Erythematosus (SLE)
SLE is a major focus for cell therapy research, with multiple studies exploring different technologies, including off-the-shelf iPSC-derived cells, dual-targeting CAR-T cells, and allogeneic CAR-NK cells.
OP0032 (Fate Therapeutics): TREATMENT OF REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS WITH OFF-THE-SHELF IPSC-DERIVED ANTI-CD19 CAR T-CELL THERAPY
Number of Patients: 3
Results: In the first three patients treated with FT819, an off-the-shelf iPSC-derived CAR-T product, rapid and deep peripheral B cell depletion was observed. The therapy was well-tolerated, with no reports of severe adverse events, cytokine release syndrome (CRS), or neurotoxicity (ICANS). All patients showed improvements in SLEDAI-2K, PGA, and fatigue scores. The first patient, who had biopsy-proven lupus nephritis, achieved DORIS clinical remission and a low lupus disease activity state by month 6, enabling the discontinuation of corticosteroid therapy.
Conclusion: Preliminary data indicate that this off-the-shelf CAR T-cell therapy has a favorable safety profile and shows promising initial efficacy in refractory SLE. These findings support its continued evaluation in SLE and other B-cell-mediated autoimmune diseases.
OP0074 (Gracell Biotechnologies/AstraZeneca): PRELIMINARY RESULTS OF CD19/BCMA DUAL-TARGETING FASTCAR-T CELLS GC012F (AZD0120) IN PATIENTS WITH REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS-AN OPEN-LABEL, SINGLE-ARM STUDY
Number of Patients: 10
Results: Ten patients with refractory SLE and lupus nephritis received the dual-targeting CAR-T therapy, GC012F. The treatment demonstrated a favorable safety profile, with only Grade 1 or 2 CRS and no high-grade CRS or ICANS reported. Robust CAR-T cell expansion and complete B-cell depletion were observed in all patients, with subsequent B-cell recovery dominated by naïve B cells. Clinically, 9 out of 10 patients achieved DORIS remission by month 9, and all showed a significant reduction in proteinuria. Seven patients were able to stop glucocorticoids completely.
Conclusion: The dual-targeting CAR-T therapy, GC012F, induced disease remission in refractory SLE patients with an early favorable safety profile. A multicenter phase 1/2 study is now ongoing to further evaluate this therapy.
OP0079 (Novartis): CLINICAL, CELLULAR KINETICS, PHARMACODYNAMICS AND BIOMARKER DATA UP TO 12 MONTHS AFTER YTB323 (RAPCABTAGENE AUTOLEUCEL), A RAPIDLY MANUFACTURED CD19 CAR-T THERAPY, FROM AN OPEN-LABEL, PHASE 1/2 STUDY IN SEVERE REFRACTORY SLE
Number of Patients: 13
Results: In 13 patients with severe refractory SLE, treatment with YTB323 was generally well-tolerated, with manageable Grade 1/2 CRS and a single Grade 2 ICANS event that resolved. All patients experienced expected transient cytopenias. In the first three patients with at least 9 months of follow-up, a marked improvement in disease activity was observed (mean SLEDAI-2K decrease of 14.7 points), along with a decrease in anti-dsDNA antibodies and an increase in complement levels. Pharmacodynamic data showed effective B-cell depletion followed by recovery of a predominantly naïve B-cell phenotype.
Conclusion: Treatment with YTB323 resulted in improved disease activity and effective B-cell depletion. The early clinical data suggest remarkable efficacy and a manageable safety profile, supporting the continued evaluation of this rapidly manufactured CAR-T therapy for severe refractory SLE.
LB0009 (Rui Therapeutics, Nanjing, China): ALLOGENIC CD19 CAR NK CELL THERAPY IN REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS-A CASE SERIES STUDY
Number of Patients: 24
Results: In a study of 24 patients with relapsed or refractory SLE, allogeneic CD19 CAR-NK cell therapy was administered. The maximum tolerated dose was not reached. CRS was mild (Grade 1) and occurred in only two patients (8%). No neurotoxicity or other severe adverse events related to the therapy were observed. Among the 12 patients with at least 12 months of follow-up, 66.7% achieved DORIS remission and 75% achieved LLDAS.
Conclusion: The study supports allogeneic CAR-NK cell therapy as a potent and safe option for treating autoimmune diseases like SLE. This approach may address some of the limitations of autologous CAR-T cell therapy, such as manufacturing time, access, and cost.
Systemic Sclerosis (SSc)
Cell therapies are being explored in SSc, a condition with high unmet need, focusing on safety and impact on skin and organ involvement.
OP0338 (Cabaletta Bio): RESET-SSCTM: CLINICAL TRIAL EVALUATING RESE-CEL (RESECABTAGENE AUTOLEUCEL), A FULLY HUMAN, AUTOLOGOUS 4-1BB ANTI-CD19 CAR T CELL THERAPY IN SYSTEMIC SCLEROSIS
Number of Patients: 1
Results: The first patient treated in this trial tolerated the rese-cel infusion well, experiencing a manageable Grade 2 CRS that resolved without tocilizumab, and no ICANS. The patient has maintained a drug-free response through 3 months, with the modified Rodnan skin score (mRSS) improving from 42 to 34. Lung function (FVC and DLCO) also improved. CAR-T cells expanded and were then cleared from the periphery, while B-cells were rapidly depleted from both peripheral blood and lymph node tissue, followed by repopulation with naïve B-cells.
Conclusion: Initial data from the first SSc patient demonstrates an early clinical response without ongoing immunosuppression and a favorable safety profile. The findings suggest rese-cel has the potential to reset the immune system in SSc.
POS0656 (Bristol Myers Squibb): TOLERABILITY AND EFFICACY OF BMS-986353 (CC-97540), A CD19-DIRECTED CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY...FOR SYSTEMIC SCLEROSIS...
Number of Patients: 5
Results: Five patients with SSc were treated with BMS-986353. The treatment was generally well-tolerated; one patient experienced a Grade 3 headache related to the therapy. Three patients had Grade 1/2 CRS, and one had Grade 1 ICANS, all of which resolved. No prolonged severe cytopenias or serious infections were reported. In three patients with diffuse cutaneous SSc, the mRSS was reduced by 15, 13, and 0 points at the last follow-up. All patients showed complete B-cell depletion and robust CAR-T cell expansion.
Conclusion: In patients with severe refractory SSc, BMS-986353 demonstrated a manageable safety profile with brief and reversible CRS/ICANS events. Preliminary data suggest promising efficacy in improving skin scores.
Idiopathic Inflammatory Myopathies (IIM)
Early trial data for CAR-T therapy in IIM shows potential for rapid, drug-free clinical responses.
OP0316 (Cabaletta Bio): RESET-MYOSITISTM: CLINICAL TRIAL EVALUATING RESE-CEL (RESECABTAGENE AUTOLEUCEL), A FULLY HUMAN, AUTOLOGOUS 4-1BB ANTI-CD19 CAR T CELL THERAPY IN IDIOPATHIC INFLAMMATORY MYOPATHIES
Number of Patients: 3
Results: The first three patients (two with IMNM, one with DM) tolerated rese-cel well, with no CRS, ICANS, or dose-limiting toxicities observed. One patient with IMNM achieved a moderate Total Improvement Score (TIS) response by Week 24 while remaining off all therapies. The patient with DM showed a rapid and robust major TIS response by Day 29, which was maintained to Week 12. In all three patients, CAR-T cells expanded and peripheral B-cells were rapidly depleted, followed by repopulation with naïve B-cells at 8 weeks in two patients.
Conclusion: Data from the first IIM patients dosed with rese-cel demonstrate early, immunomodulatory-free clinical responses and a favorable safety profile. These results suggest the potential for rese-cel to reset the immune system and achieve meaningful clinical responses in IIM.
Rheumatic Diseases (Multi-Disease Basket Trial)
A basket trial including patients with SLE, SSc, and IIM demonstrates the broad potential and consistent safety profile of CAR-T therapy across different rheumatic diseases.
POS0062 (Erlangen university lead): SAFETY AND PRELIMINARY EFFICACY OF CD19 CAR T-CELL TREATMENT IN RHEUMATIC DISEASE – DATA FROM THE PHASE I/II CASTLE BASKET STUDY
Number of Patients: 20
Results: In a cohort of 20 patients (8 SLE, 8 SSc, 4 IIM), no high-grade (≥3) CRS or any ICANS were observed. Late-onset grade 3/4 neutropenia occurred in 4 SLE patients but resolved. Three severe infections were reported. All seven SLE patients with 6-month follow-up achieved DORIS remission. Both IIM patients achieved a moderate/major ACR response. All six SSc patients showed improvement in skin scores without worsening of lung function. All patients remained off their prior immunosuppressive drugs and glucocorticoids after CAR-T therapy.
Conclusion: The data from this basket study underline the safety and preliminary efficacy of CD19 CAR T-cell therapy across different severe autoimmune diseases, with no unexpected toxicities and promising clinical responses in all three disease groups.
General / Preclinical Cell Therapy Research
Research into novel CAR-T and cell therapy platforms continues to advance, with a focus on improving safety, manufacturing, and efficacy for broad application in autoimmune diseases.
POS0876 (Kyverna Therapeutics): EFFECT OF ANTI-CD19 CAR T CELL THERAPY IN THE BONE MARROW OF PATIENTS WITH SYSTEMIC AUTOIMMUNE DISEASES
Number of Patients: 3
Results: In three patients with severe, treatment-resistant autoimmune diseases, anti-CD19 CAR T-cell therapy was safe and led to stable clinical improvement. Bone marrow biopsies performed after therapy but before peripheral B-cell return showed that B cells, especially CD19+ plasmablasts and plasma cells, were significantly reduced. In one patient evaluated after B-cell reconstitution, the bone marrow B cells were predominantly of a naïve/transitional phenotype, with memory B cells and plasmablasts remaining diminished.
Conclusion: Anti-CD19 CAR T-cell therapy promotes remission by effectively depleting B-cell populations within primary lymphatic organs like the bone marrow, a key site for long-lived plasma cells.
POS1402 (Fate Therapeutics): A NOVEL PLATFORM... FUNCTIONALLY ENHANCED... CD19 CAR-T THERAPY FOR AUTOIMMUNE DISEASE
Number of Patients: 1 (in oncology proof-of-concept)
Results: Preclinical data showed the investigational therapy FT522, an off-the-shelf iPSC-derived CAR-NK cell product, was capable of rapid and potent depletion of B cells from SLE donors in vitro. Early data from a Phase 1 trial in B-cell lymphomas, where FT522 was administered without conditioning chemotherapy, showed the product could persist and function. In a patient with Waldenstrom Macroglobulinemia, this resulted in clinical benefit, including a significant reduction of IgM.
Conclusion: Preclinical and early oncology clinical data demonstrate that FT522 can persist and function and confer clinical benefit without the need for conditioning chemotherapy. This supports its potential application for B-cell mediated autoimmune diseases, with a Phase 1 trial in this setting planned.
ABS0179 (Universit. Vita Salute San Raffaele, Milan, Italy): UNDERSTANDING CAR-TREG PERSISTENCE AND EXPANSION PROTOCOLS OPTIMIZATION
Number of Patients: No patients
Results: Using a humanized mouse model of SLE, this study confirmed that CAR-Treg cells showed an initial expansion followed by contraction, disappearing from peripheral blood after 39 days. The therapy was safe, with no CRS or B-cell aplasia. The study successfully identified an optimized CAR-Treg expansion protocol using a re-stimulation step, which significantly increased cell expansion without compromising phenotype or suppressive function.
Conclusion: The study successfully tracked CAR-Tregs in vivo and identified an improved method for their expansion, which is critical for optimizing their therapeutic potential and persistence for future clinical applications.
ABS0750 (iCell Gene Therapeutics Inc.): FIRST USE OF NOVEL BCMA AND CD19 NANOBODY-BASED COMPOUND CAR-T THERAPY TO TARGET B-CELLS AND PLASMA CELLS IN PRECLINICAL STUDY OF AUTOIMMUNE DISEASES
Number of Patients: 1 (compassionate use case)
Results: A novel BCMA-CD19 compound CAR-T therapy using camelid nanobodies (ncCAR) showed potent killing of target cells in vitro and effective depletion in mouse models. In a compassionate use case, a patient with multiple myeloma and immune thrombocytopenia (ITP) achieved stringent complete remission of their cancer and complete resolution of thrombocytopenia with normalization of platelet counts, demonstrating remarkable safety and efficacy.
Conclusion: This first-in-human use of ncCAR therapy demonstrated exceptional preclinical and clinical efficacy. The ability of the dual-targeting therapy to resolve ITP validates its potential to deplete the humoral cells that drive autoimmune disease, supporting its investigation for conditions like SLE.