[T-cell engagers: a transformative force or a redundant option in B-cell depletion therapy for rheumatic diseases?]

The treatment of rheumatic diseases (RMD) is still challenged by long-term treatment dependence and refractory relapses. Therapeutic goals are therefore shifting from suppression of inflammation toward deep B-cell depletion and immune resetting. Conventional B-cell-depleting monoclonal antibodies have insufficient capacity for tissue B-cell depletion. Autologous chimeric antigen receptor T-cell (CAR-T) therapy has shown the potential for deep immune reconstitution, but its clinical use is constrained by individualized manufacturing, lymphodepleting conditioning, cost, and safety-management requirements. T-cell engagers (TCE) simultaneously bind cluster of differentiation (CD) 3 on T cells and target antigens on B cells or plasma cells. They redirect endogenous T cells to eliminate pathogenic target cells. TCE can offer the advantages of standardized manufacturing, no requirement for ex vivo cell preparation, and flexible adjustment of dose and treatment duration. Focusing on the latest advances in TCE therapy for rheumatic diseases, this review systematically summarizes studies targeting CD19, CD20, and B-cell maturation antigen (BCMA). Available evidence indicates that TCE can rapidly deplete B cells or plasma cells in systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, and rheumatoid arthritis, and may reduce disease activity and promote remission. The main adverse events include cytokine release syndrome, infections, and hypogammaglobulinemia, most of which appear manageable. Accordingly, the clinical value of TCE in rheumatic diseases is becoming increasingly apparent. However, several key issues remain to be resolved, including the depth of tissue B-cell depletion, the quality of immune reconstitution, endogenous T-cell fitness, mechanisms of inadequate response, and long-term safety. TCE therapy is neither a costly duplication of existing B-cell-depleting therapies nor a definitive solution for immune resetting. Rather, it represents a more accessible and clinically manageable therapeutic approach that may offer a practical route toward immune resetting in RMD.