October 5, 2026
Naunyn Schmiedebergs Arch Pharmacol – 2025 Aug 14;399(2):1565–1588. doi: 10.1007/s00210-025-04425-z
Omima Ahmed Sayed1,#, Mohamed Ellebedy2,✉,#, Mohamed Ahmed Abu-Alsaud3, Amro Issam Bakri Meligy4, Tamer A Gheita5
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PMCID: PMC12901168 PMID: 40813483
Abstract
Conventional therapies for systemic lupus erythematosus (SLE) often fail to achieve lasting remission. CAR T cell therapy, which depletes autoreactive B cells, offers a novel approach for refractory cases. We aim to consolidate the current evidence on CAR T cell therapy in the treatment of SLE. PubMed, Scopus, Web of Science, the Cochrane Library, and Clinical trials.gov were searched up to November 18, 2024, for SLE patients receiving CAR T cell therapy. Data on efficacy, safety, and treatment responses were analyzed. Ten studies involving 47 SLE patients were identified. Among those patients, 81% achieved lupus low disease activity state (LLDAS) with improvements in disease activity and serologic markers. B cell depletion was consistent, with immune recovery over time. Cytokine release syndrome (CRS) occurred in 87% but was mostly mild (grades 1–2). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred only in one patient and was mild (grade 1). CAR T cell therapy shows promise in refractory SLE, achieving durable remission with manageable toxicity. Further trials are needed to confirm long-term outcomes.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00210-025-04425-z.
Keywords: CAR T cell therapy, Systemic lupus erythematosus, Systematic review
Introduction
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell dysfunction, leading to production of autoantibodies which play a pivotal role in the initiation and progression of disease. Managing SLE patients remains a therapeutic challenge due to its complex immunopathogenesis (Feng et al. 2020; Arnaud et al. 2024). Historically, SLE management relied on antimalarials, corticosteroids, and traditional immunosuppressants, which are effective in suppressing the ongoing inflammatory process but do not address the underlying immune dysfunction. The advent of biologic therapies has introduced more targeted approaches to treatment, but achieving sustained remission remains challenging (Ruiz-Irastorza and Bertsias 2020; Basta et al. 2020). Many SLE patients either experience refractory disease leading to marked morbidity or suffer from adverse effects associated with prolonged immunosuppression (Urowitz et al. 2012).
The emergence of chimeric antigen receptor (CAR) T cell therapy represents a paradigm shift in immunotherapy. Originally developed for hematologic malignancies, CAR T cell therapy involves the genetic modification of T cells to express receptors specific to antigens present on B cells. This approach targets and depletes pathogenic autoreactive B cells while sparing other components of the immune system, offering a potentially more targeted and durable therapeutic option compared to conventional B cell-depleting biologics. Given its ability to penetrate tissues more deeply, CAR T cell therapy has the theoretical advantage of achieving more comprehensive B cell depletion resulting in a “deep remission” state (Schett et al. 2023; Kretschmann et al. 2023; Lyu et al. 2024; Guffroy et al. 2024).
Preclinical models and early-phase clinical trials have demonstrated promising results with CAR T cell therapy in SLE, including significant clinical responses in patients with refractory disease (Mackensen et al. 2022; Jin et al. 2021). These findings suggest that CAR T cell therapy may represent an upgrade in the management of SLE, offering a promise to reset the immune dysregulation and as a result a drug-free remission. Despite encouraging preliminary findings, critical questions remain regarding the long-term safety, efficacy, and durability of response to CAR T cell therapy in SLE. This systematic review aims to consolidate current evidence on CAR T cell therapy in the context of SLE.
Methodology
Data sources and search strategy
Our systematic review was executed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Page et al. 2021). As this analysis was based on previously published studies, ethical approval and patient consent were not required. We conducted a systematic search of five electronic databases, PubMed, Scopus, Web of Science, the Cochrane Library, and Clinical trials.gov to identify relevant literature published up to November 18, 2024. Our search strategy employed a combination of keywords and medical subject headings (MeSH) combined with Boolean operators “AND” and “OR” to ensure comprehensive coverage of the literature. Specifically, we used the following search terms: (“CAR T cells” OR “CAR T-cells” OR “chimeric antigen receptor T Cell” OR “chimeric antigen receptor T-Cell” OR “chimeric antigen receptor T-lymphocyte” OR “chimeric T-Cell Receptor” OR “CAR-T cell therapy” OR “CAR-T therapy” OR “CAR-T”) AND (“systemic lupus erythematosus” OR SLE OR “lupus” OR “autoimmune disease” OR “autoimmune disorder”). The search strategy was adjusted to meet the requirements of each database. The results were imported into Rayyan software, a platform designed to facilitate the systematic review process, especially for screening and selecting studies.
Study selection and eligibility criteria
The inclusion criteria were based on the Population, Intervention, Comparator and Outcome (PICO) framework (Schardt et al. 2007). Two independent investigators assessed all articles at the title and abstract level, after which the full text was read to confirm relevance. The conflicts were resolved by discussion. Only primary studies reporting SLE patients receiving CAR T cell therapy were included. There were no restrictions regarding geographical region or publication date of the included articles. The reference lists of retrieved studies were hand-searched to include additional eligible studies.
Data extraction
Data from the included studies were extracted and recorded in a Microsoft Excel spreadsheet, which contained the following study information: study ID (first author’s last name and year of publication), study design, site, date of CAR T cell infusion, sample size, number of females and their percentage, age (in years), SLE duration (range; median), type of CAR T cells, dose, and follow-up duration. Additionally, we collected patient-by-patient data, including age (in years), sex, SLE duration (in years), organ involvement, type of CAR T cells, dose, follow-up duration (in days), previous medications including the prior use of anti B cell therapies, CAR T cell expansion, and the day of its peak, SLEDAI-2K (baseline and at the end of follow-up), physician global assessment (PGA), ability to discontinue all SLE-related medications, and achievement of LLDAS (lupus low disease activity state) or DORIS (Definitions of Remission in SLE), anti-dsDNA, and complement levels, cytokine release syndrome (CRS) and its grade, management of CRS, and immune effector cell-associated neurotoxicity syndrome (ICANS). For ongoing trials, we extracted the following information for each trial: ClinicalTrials.gov ID, phase, start date, intervention, target number of participants, and trial status.
Statistical analysis
Since this review is primarily descriptive, we utilized descriptive statistics, reporting means or medians for continuous variables and frequencies with percentages for categorical variables.
Risk of bias assessment
The quality of included case reports was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for case reports (Munn et al. 2020), covering patient demographics, clinical history, presentation, diagnostics, interventions, post-intervention outcomes, adverse events, and takeaway lessons. Wang et al. and Muller et al. were assessed using the JBI Critical Appraisal Checklist for case series (15), evaluating inclusion criteria, measurement reliability, identification methods, participant inclusion, demographic and clinical data reporting, outcome reporting, site demographic reporting, and statistical analysis. Risk of bias (ROB) was independently evaluated by two investigators, with discrepancies resolved through discussion. Conference abstracts were excluded from quality assessment.
Results
Search results
Our search strategy identified 725 studies from PubMed (n = 171), Scopus (n = 281), Web of Science (n = 147), Cochrane Library (n = 3), and Clinical trials.gov (n = 123). A total of 270 duplicate articles were removed, followed by the exclusion of 359 studies during the title and abstract screening. After full-text screening, ten studies (11 reports) and 68 clinical trials were included in this systematic review (Fig. 1).
Study characteristics
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