Bispecific-Antibodies

Ten patients with severe, treatment-refractory systemic sclerosis were given teclistamab, a BCMA × CD3 bispecific T cell engager approved for myeloma, off label. B cells and plasma cells almost disappeared from bone marrow and skin, anti-topoisomerase titres fell by a median of 70.6%, and skin, lung and cardiac measures improved within 12 weeks. The price was universal severe hypogammaglobulinaemia, frequent infections and two deaths in patients with advanced heart disease, in a small, retrospective, uncontrolled series.

Fifteen patients with multidrug-resistant RA received blinatumomab at roughly a tenth of the haematology dose. All 15 achieved at least ACR20 and synovial B cells were depleted, but 14 of 15 flared within a median five months. The more provocative observation is what happened next: seven patients responded for over three months to b/tsDMARDs that had already failed them — raising the possibility that partial depletion resensitises rather than resets.

A 2026 narrative review of T-cell engagers (TCEs) in autoimmune rheumatic disease — off-the-shelf bispecific antibodies that redirect a patient’s own T cells against autoreactive B/plasma cells, pitched as a repeatable, dose-adjustable alternative to CAR-T. Early efficacy across SLE, SSc, RA, myositis and Sjögren’s is real but preliminary, and the review’s headline problem is under-dosing relative to oncology, which likely drives frequent relapse.