CD19×CD3 bispecific T cell engager treatment induces remission in experimental pemphigoid disease

Pemphigoid diseases (PDs) are autoimmune disorders marked by autoantibodies (Aabs) against skin and mucous membrane proteins, causing mucocutaneous blistering in predominantly elderly patients. Since current therapeutics are often insufficient, PDs impose a significant morbidity and mortality burden. CD19×CD3 bispecific T cell engagers (TCEs)-originally developed for B cell malignancies-have shown promise in treatment-refractory autoimmune diseases such as systemic sclerosis and rheumatoid arthritis. To explore their potential in PDs, we tested a murine CD19×CD3 TCE in a mouse model of epidermolysis bullosa acquisita (EBA), a prototypical PD. The TCE selectively depleted B cells in the blood and bone marrow, but not the spleen, of healthy mice. Mice with clinically manifest immunization-induced EBA were randomized to receive either the CD19×CD3 TCE or control treatment upon reaching a predefined disease severity. After 13 weeks, 45% of TCE-treated mice achieved remission, vs. 23% of controls. This improvement correlated with reduced antigen-specific B cells, although total and antigen-specific IgG levels were unchanged. These findings suggest that CD19×CD3 TCEs preferentially target autoreactive B cells and may be effective at lower doses than those used in oncology. Our data support the potential of CD19×CD3 bispecific TCEs as a therapeutic strategy for PDs.