T-cell engagers have demonstrated remarkable potency in oncology, but in autoimmune diseases they aim to achieve sufficient target-cell killing without triggering cytokine release profiles that are unacceptable in chronic outpatient populations. This technical workshop will explore the molecular architecture, construct design, and developability considerations that underpin next generation autoimmune TCEs by:

• Evaluating CD3 tuning as a molecular design strategy rather than a clinical mitigation tool, examining how affinity modulation, epitope selection, valency, and spatial geometry influence T-cell activation thresholds
• Identifying the structural determinants of efficacy-versus-cytokine separation, to understand construct formats that may uncouple cytotoxic activity from systemic T-cell hyperactivation
• Optimizing engager architecture for autoimmune applications, exploring how binder orientation, domain arrangement, linker design, avidity effects, and target-antigen biology influence immune synapse formation, pharmacology, and safety outcomes