CAR-based cellular therapies for autoimmune diseases: immune reset, clinical evidence, and translational boundaries.

Emerging targeted therapies for primary immune thrombocytopenia: novel agents, combination strategies, and future directions

An autoimmune disease with notable clinical variability, primary immune thrombocytopenia is typified by immune-mediated platelet underproduction and destruction. Conventional therapies, including glucocorticoids and splenectomy, are limited by adverse effects, high relapse rates, and surgical risks. Recently, with the in-depth study of immune thrombocytopenia, new targeted drugs have emerged rapidly. We conducted a systematic literature search of PubMed, Web of Science, and ClinicalTrials.gov from May 2010 up to May 2026, using search terms related to “immune thrombocytopenia” AND “targeted therapy” OR “novel agents.” Eligible studies included phase I–III clinical trials, prospective observational studies, and high-quality preclinical mechanistic studies evaluating novel ITP therapeutics, while case reports and editorials were excluded. Two independent reviewers screened titles and abstracts, followed by full-text assessment, with discrepancies resolved by consensus. Given the heterogeneous nature of the included evidence, we adopted a narrative synthesis approach, complemented by a clinical evidence-grading framework that stratified emerging agents by the maturity of their supporting data (phase I, phase II, phase III, or preclinical studies), rather than performing a quantitative meta-analysis. This article analyses recent therapeutic trials with Bruton’s tyrosine kinase inhibitors, splenic tyrosine kinase inhibitors, and neonatal Fc receptor antagonists, demonstrating an improvement in platelet counts and patients’ quality of life. Furthermore, combination therapy regimens show great promise in terms of synergistic effects, while cellular therapies, such as chimeric antigen receptor T-cell immunotherapy and mesenchymal stem cell therapy, appear to offer new treatment concepts for patients with persistent, chronic, refractory, or multi-refractory ITP. However, there are still many problems and shortcomings in the diagnosis and treatment of immune thrombocytopenia. In addition, the transition from preliminary evidence to routine clinical application requires larger phase III confirmatory studies, validated biomarker-driven patient selection, and context-adapted treatment algorithms that address resource-limited settings. Future research should prioritize head-to-head comparisons, combination regimens, and real-world effectiveness studies to optimize long-term outcomes for all ITP patients.

Targeting CD38 Across Autoimmune and Plasma Cell-Driven Immune-Mediated Diseases: Rationale, Clinical Evidence, and Emerging Therapeutic Landscape.

Autoimmune diseases remain a major cause of chronic morbidity despite substantial advances in targeted immunomodulatory therapies. In many autoantibody-mediated conditions, disease refractoriness and relapse are driven by long-lived plasma cells, which are largely resistant to conventional immunosuppression and upstream B cell-directed strategies. CD38, a surface molecule highly expressed on plasmablasts and plasma cells and functionally involved in immunometabolic regulation, has emerged as a promising therapeutic target to overcome this limitation. Clinical interest in anti-CD38 therapy has been catalyzed by experience in plasma cell dyscrasias, where anti-CD38 monoclonal antibodies induce rapid and profound depletion of antibody-secreting cells. Over recent years, accumulating reports and early-phase studies have explored the repurposing of CD38-directed therapies in severe, treatment-refractory autoimmune diseases. The most compelling evidence has emerged in lupus nephritis and immune thrombocytopenia, with additional proof-of-concept data in autoimmune cytopenias and plasma cell-driven renal disorders such as immunoglobulin light chain (AL) amyloidosis. These experiences suggest that targeting CD38 can lead to meaningful clinical and immunological improvement, often accompanied by rapid reductions in pathogenic autoantibody production. However, the current evidence base remains heterogeneous and largely derived from small cohorts, case series, and early-phase trials, and important questions remain regarding durability of response, optimal treatment strategies, and long-term safety, particularly with respect to hypogammaglobulinemia and infection risk. We summarize the biological rationale for CD38 targeting in autoimmunity and plasma cell-driven immune-mediated diseases, critically appraise the emerging clinical evidence across disease settings, and discuss key challenges and future directions for integrating plasma cell-directed therapies into immunological disease management.

CAR-T cell therapy for autoimmune diseases: from immune suppression to immune resetting.

Autoimmune diseases are heterogeneous disorders marked by immune dysregulation, loss of self-tolerance, autoantibody production, and chronic inflammation. Although immunosuppressants and biologics have improved disease control, incomplete remission, relapse after withdrawal, cumulative toxicity, and failure to restore immune homeostasis remain common. Chimeric antigen receptor T-cell (CAR-T) therapy offers a potential strategy for refractory autoimmune diseases by selectively eliminating pathogenic immune compartments and providing a theoretical pathway toward target-dependent immune remodeling and immune resetting. This review summarizes immunopathogenesis and therapeutic gaps in representative autoimmune diseases, compares CAR-T applications in malignancies and autoimmunity, and evaluates emerging response endpoints, target-selection strategies, and safety considerations in autoimmune settings. Early clinical evidence suggests rapid disease control, autoantibody reduction, and immunosuppression-free remission in selected B-cell- or autoantibody-driven diseases. However, reported remission duration and response proportions remain limited by small cohorts, short follow-up, and disease-specific heterogeneity. The central unresolved question is whether durable remission can be achieved without persistent immune deficiency. Cytokine release syndrome, infection, hypogammaglobulinemia, relapse, impaired vaccine responses, T-cell fitness, manufacturing barriers, and cost remain key challenges. Future studies should define optimal targets, standardized remission endpoints, durable remission biomarkers, long-term safety, and the role of T-cell engagers.

CD19 CAR T cell therapy for treatment-refractory seropositive rheumatoid arthritis: a phase 1 trial.

The Pharmacology of CAR T Cell Therapy for Autoimmune Disease.

In autoimmune diseases, cell-based therapies exemplified by CAR T cells should be reframed from exposure-control pharmacology to state-transition pharmacology, and through endogenous expansion and immune networks, therapeutic cells may shift the immune system from a pathological toward a tolerant steady state.

The role and potential of CD19-targeted chimeric antigen receptor T-cell therapy in systemic sclerosis

Systemic sclerosis (SSc) remains a challenge due to high mortality and resistance to treatment. Chimeric antigen receptor T-cell (CAR-T) technology (anti-CD19) may offer an opportunity for an immune system reset and long-term disease remission, eliminating the need for lifelong medication. This narrative review is based on a literature search in the PubMed and Scopus databases from 2023 to 2026. The main search phrases were: “CAR-T in systemic sclerosis”, “CAR-T scleroderma”, and “CAR-T SSc.” CD19-targeted CAR-T therapy led to significant clinical improvement across analyzed cases. The median modified Rodnan skin score decreased by 8–13 points within 3–6 months. Disease activity, measured by the European Scleroderma Trials and Research Group Activity Index (EUSTAR-AI), showed a mean improvement ranging from 2.1 to 4.2 points. Pulmonary function remained stable or improved, with forced vital capacity increasing by up to 7% in responders. The safety profile was manageable, primarily consisting of grade 1 cytokine release syndrome in approximately 75–80% of patients. CD19-targeted CAR-T therapy is a promising investigational option for patients with refractory SSc. Limitations include small study groups and a lack of randomized controlled trials, warranting further validation in ongoing clinical studies.