T cell engagers emerge as a compelling therapeutic modality

T cell engagers (TCEs) are antibody-based constructs designed to transiently reprogram cytotoxic T lymphocytes for target cell elimination by simultaneously binding the T cell receptor and a specific surface antigen on the target cell. Over the past 12 years, 10 TCEs were approved by the US Food and Drug Administration, and an additional two by the European Medicines Agency. Nine TCEs treat hematologic malignancies, and three target solid tumors. Over 150 TCEs are being investigated in clinical trials, recently also in autoimmune diseases. Here, we discuss the learnings from the 12 approved TCEs. A surprising variety of molecular designs and biochemical characteristics appear suitable for approval. On the clinical side, we review targets, indications, dosing, schedules, side effects, mitigation strategies for adverse events, and efficacy. High flexibility in design and choice of target, scalability, high response rates as a monotherapy in hematologic malignancies, and emerging efficacy against solid tumors and in autoimmune diseases make TCEs an attractive therapeutic modality.