CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives.

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) are debilitating autoimmune disorders characterized by pathological autoantibodies production and immune dysfunction, causing chronic inflammation and multi-organ damage. Despite current treatments with antimalarial drugs, glucocorticoids, immunosuppressants, and monoclonal antibodies, a definitive cure remains elusive, highlighting an urgent need for novel therapeutic strategies. Recent studies indicate that chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in treating B-cell malignancies and may offer a significant breakthrough for non-malignant conditions like SLE.

The persistence and antitumor efficacy of CAR-T cells are modulated by tonic signaling within the CDR.

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable clinical efficacy, but challenges related to relapse and CAR-T cell exhaustion persist. One contributing factor to this exhaustion is CAR tonic signaling, where CAR-T cells self-activate without antigen stimulation, leading to reduced persistence and impaired antitumor activity. To address this issue, we conducted a preclinical study evaluating tonic signaling using nanobody-derived CAR-T cells.