[From CAR-T to T-cell engagers : New T-cell-based treatment in rheumatology]

Cellular forms of treatment mark a paradigm shift in the treatment of autoimmune diseases. While conventional and targeted antirheumatic treatment controls disease activity mostly by continued immunomodulation, innovative cellular approaches, especially chimeric antigen receptor (CAR) T‑cells targeting CD19, target a deep elimination of disease-relevant immune cell compartments with subsequent immunological reconstitution. This concept of an immune reset is particularly attractive for those diseases in which autoreactive B‑cells, plasmablasts, autoantibodies and misdirected lymphocyte networks are pathogenetically central. In addition, T‑cell engagers or bispecific T‑cell engagers (TCE) are now becoming of interest, which as off the shelf strategies without cellular production also enable a deep B‑cell or plasma cell depletion via T cell-mediated cytotoxicity. The most impressive clinical data so far are available for systemic lupus erythematosus (SLE), likewise accumulating indications for the efficacy in systemic sclerosis (SSc) and idiopathic inflammatory myositis (IIM). The concept is highly plausible for rheumatoid arthritis (RA) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) but is clinically still in an early developmental stage. Initial clinical experiences are available for TCE, especially for refractory RA and for severe connective tissue diseases, including SSc and antisynthetase syndrome. The evidence for other rheumatological indications is so far much more limited. This article discusses the biological principles, production and mechanisms of action, the revolutionary potential of these strategies, current evidence in selected rheumatological indications and open questions on safety, patient selection and future perspectives.