As autoimmune T-cell engagers move beyond first-generation designs, many developers are encountering a common challenge, exhausted and dysfunctional T cells may limit the depth and durability of clinical responses. Co-stimulatory approaches have emerged as a promising strategy to enhance T-cell fitness, persistence, and efficacy, but questions remain around how much co-stimulation is needed and how to balance improved potency with cytokine release and safety risks.

This panel will discuss how co-stimulation could reshape the future of autoimmune therapy by:

• Understanding the biology of T-cell exhaustion and persistence, exploring the mechanisms driving reduced T-cell functionality in autoimmune patients and identifying opportunities to restore effective immune responses
• Evaluating emerging co-stimulatory strategies, comparing approaches leveraging CD28, CD2, 4 1BB, and other pathways to determine how they influence efficacy, durability, immune-cell depletion, and safety profiles
• Defining the optimal balance between potency and safety, discussing how co-stimulation can be integrated into nextgeneration engager designs to maximize clinical benefit while minimizing cytokine release syndrome, off-target activation, and long-term immune suppression