Bispecific T-cell engagers in autoimmune diseases: mechanisms of action, clinical evidence challenges, and therapeutic perspectives.

Bispecific T-cell engagers (TCEs) represent a new generation of immunotherapies designed to redirect cytotoxic T lymphocytes toward specific cellular targets, particularly B cells and their differentiated progeny. Initially developed in hematology for the treatment of malignant B-cell and plasma-cell disorders, TCEs are now gaining growing interest as potential therapies for severe or refractory autoimmune diseases. By simultaneously binding CD3 on T cells and antigens such as CD19, CD20, or BCMA (B-cell maturation antigen) on B-lineage cells, TCEs induce the targeted elimination of autoreactive B cells and plasma cells responsible for autoantibody production. This approach combines the depth of immune depletion achieved with cellular therapies and the controllability of monoclonal antibodies, offering the potential for rapid, profound, and durable immunomodulation. However, it also raises important questions regarding safety, feasibility, and cost. Compared with CAR-T cell therapies, TCEs offer a more accessible and immediately deployable strategy, while potentially achieving comparable levels of B-cell and plasma-cell depletion, though with shorter exposure and possibly reduced long-term persistence. This review provides an integrated overview of mechanistic, preclinical, and emerging clinical data on the use of TCEs in autoimmune diseases, and discusses their therapeutic potential, and limitations in this evolving field.