NEW early clinical evidence suggests that allogeneic CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy may induce sustained remission in patients with severe, refractory systemic lupus erythematosus (SLE), marking a potential breakthrough for individuals who fail conventional immunosuppressive treatments.
SLE is driven in part by autoreactive B cells, which produce pathogenic autoantibodies and perpetuate immune dysregulation. While B-cell–directed therapies such as rituximab and belimumab have improved outcomes for some patients, many with severe, multi-organ disease remain difficult to treat. CAR-T cell therapy, which has transformed outcomes in certain haematological malignancies, is now being explored as a strategy to more profoundly reset pathological immune responses in autoimmune disease.
First-in-Field Allogeneic CAR-T Approach
In this prospective study, three patients with severe, refractory SLE and multi-organ involvement received a single intravenous infusion of genetically engineered CD19-targeting CAR-T cells derived from healthy donors. The cells were administered at a dose of 1 million cells per kilogram, and patients were followed for up to 12 months.
The primary aim was to assess safety, with particular attention to complications commonly associated with CAR-T therapy, including graft-versus-host disease, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome.
Favourable Safety Profile
Over the follow-up period, no patient developed graft-versus-host disease, cytokine release syndrome, or neurotoxicity, and no severe treatment-related adverse events were reported. CAR-positive T cells expanded in vivo, peaking around day 14 after infusion before gradually declining, consistent with effective but controlled cellular activity.
As expected, treatment resulted in profound depletion of circulating B cells, both in percentage and absolute counts, supporting the biological activity of the CAR-T cells.
One patient withdrew from the study at month 1 due to persistent severe thrombocytopenia requiring additional immunosuppressive therapy. The remaining patients completed follow-up.
Sustained Clinical Remission
Clinical efficacy assessments showed marked improvement across multiple disease activity measures. SELENA-SLEDAI and SLEDAI-2K scores declined substantially following treatment, and all patients who completed follow-up achieved clinical remission according to the SLE Responder Index-4 at their final visit. Remission was also supported by improvements in BILAG and DORIS remission indices.
The durability of response over 12 months is particularly notable in this population, where disease control is often transient despite aggressive therapy.
Implications for Lupus Treatment
Although limited by its small sample size, the study provides compelling proof-of-concept that allogeneic CAR-T cell therapy may be both safe and clinically effective in severe, refractory SLE. The absence of classic CAR-T–related toxicities is especially encouraging and may reflect differences between autoimmune and oncological applications of this technology.
The authors conclude that CAR-T therapy could represent a paradigm shift in lupus treatment by offering deep immune reset rather than incremental immunosuppression. Larger, controlled trials will now be required to confirm safety, define optimal dosing, and determine which patients are most likely to benefit from this highly innovative approach.
If validated, CAR-T therapy may open a new chapter in the management of refractory autoimmune disease, extending a technology once reserved for cancer into the realm of immune-mediated disorders.
