A novel co-infusion strategy employing both CD19– and BCMA-targeting CAR-T cells demonstrated promising initial results in a phase 1 trial for patients wiht treatment-refractory systemic lupus erythematosus (SLE), researchers report. The study, published in Nature Medicine, offers a potential breakthrough for a challenging autoimmune disease where current therapies frequently enough fall short, and represents a significant step toward precision cellular immunotherapy for SLE.
Systemic lupus erythematosus,a chronic autoimmune disease,affects an estimated 500,000 Americans,disproportionately impacting women and individuals of African,Hispanic,Asian,and Native American descent. Existing treatments, including immunosuppressants and corticosteroids, can have debilitating side effects and frequently enough fail to achieve long-term remission. This new approach aims to selectively target and deplete autoreactive B cells-key players in SLE’s pathology-while concurrently addressing antibody-secreting plasma cells, offering a dual-pronged attack on the disease.
The phase 1 trial enrolled six patients with severe, treatment-refractory SLE. participants received a single infusion of CAR-T cells targeting both CD19, found on many B cells, and BCMA, expressed on plasma cells. Preliminary data indicate the treatment was well-tolerated, with no dose-limiting toxicities observed. Cytokine release syndrome (CRS) and neurologic toxicity-potential complications of CAR-T therapy-where managed using established protocols, guided by ASTCT consensus grading (Lee, D. W. et al. Biol.Blood Marrow Transpl. 25, 625-638 (2019)).
Notably, four of the six patients achieved a clinical response, defined as a reduction in SLE Disease Activity Index 2000 (SLEDAI) scores. Two patients experienced complete remission,maintaining symptom control for at least six months following CAR-T cell infusion. B-cell depletion was observed in all patients, with varying degrees of reconstitution over time. Further examination into the durability of these responses and the long-term safety profile is ongoing.
researchers acknowledge the need for larger, randomized controlled trials to confirm these findings and optimize the CAR-T cell dosing and conditioning regimens.The safety and efficacy of autologous and allogeneic humanized CD19-targeted CAR-T cell therapy for relapsed/refractory B-ALL has paved the way for this research (Song,C. J. Immunother. cancer 11 (2023)). This early success suggests that co-targeting CD19 and BCMA may represent a viable therapeutic strategy for SLE patients who have exhausted conventional treatment options, potentially transforming the landscape of autoimmune disease management.
