[CAR-T cell therapy for systemic lupus erythematosus: immune reset or an expensive attempt?]

Abstract

In the treatment of rheumatic and autoimmune diseases in China, patients often experience relapses after discontinuing traditional immunosuppressants, and those with refractory disease continue to face the challenge of progressive organ damage. In recent years, chimeric antigen receptor (CAR-T) cell therapy has achieved breakthroughs in autoimmune diseases such as systemic lupus erythematosus (SLE). Anti-cluster of differentiation 19 (CD19) CAR-T therapy can deeply eliminate B cells, enabling some patients to maintain long-term remission without the use of immunosuppressants. This has led to the concept of "immune reset", that is, the reconstruction of the immune system starting from hematopoietic progenitor cells and the restoration of self-tolerance. Taking SLE as an example, this article analyzes the success rates and limiting factors of different CAR-T strategies in achieving immune reset, using case data from 17 clinical studies. The results show that the dual-target strategy, targeting B-cell maturation antigen (BCMA) and CD19, has clear advantages in terms of the depth and durability of immune reset, enabling some patients with refractory SLE to achieve long-term drug-free remission. However, immune reset is not universally successful, and its achievement is constrained by multiple factors, including target coverage, pre-existing organ damage, and disease-driving mechanisms. In summary, CAR-T therapy offers an effective new option with the potential for immune reset in patients with refractory SLE, but clinical application requires individualized decision-making based on the patient's specific circumstances. As evidence accumulates and technology is optimized, this strategy may become a viable option for more patients with autoimmune diseases.