T-cell engagers have transformed the treatment of hematological malignancies, and growing interest is now directed toward applying these platforms to autoimmune and immune-mediated diseases. This transition to chronic, non-life-threatening conditions fundamentally alters the risk-benefit calculus and raises critical questions about safety expectations, preclinical development, and dose selection.

• Assessing which aspects of TCE design can be directly applied from oncology to autoimmune settings and which formats must be re-engineered to optimise potency and affinity
• Reframing safety expectations in autoimmune TCEs by evaluating why oncology-derived risk-benefit frameworks are insufficient, highlighting gaps in preclinical models and aligning with evolving regulatory expectations for safer development
• Translating oncology learnings to inform study design, dose selection, risk–benefit assessment and operational considerations for TCE development in autoimmune indications