Mohamed Hassanein

While early autoimmune T-cell engager programs have demonstrated promising peripheral immune-cell depletion, many developers are now confronting a critical challenge: durable remission may require eliminating pathogenic immune cells thatreside deep within tissues, lymph nodes, bone marrow, and inflamed disease sites. Achieving meaningful tissue penetration while balancing safety, persistence, and immune preservation has emerged as one of the defining scientific hurdles for the next generation of autoimmune therapies. This panel will discuss how the field can overcome the biological barriers limiting deep and durable immune reset by:

• Understanding the mechanisms limiting tissue penetration and depletion, exploring how immune-cell localization, tissue architecture, inflammatory microenvironments, and target accessibility influence the ability of T-cell engagers to reach and eliminate pathogenic cell populations
• Advancing therapeutic strategies to improve deep tissue activity, evaluating innovations in molecule design, multispecific targeting, dosing strategies, half-life engineering, and immune-cell trafficking approaches that enhance tissue penetration while maintaining manageable safety profiles
• Developing biomarkers and translational tools to measure true immune reset, discussing how imaging, tissue biopsies, molecular profiling, and next-generation biomarker platforms can be used to assess tissue-level depletion, predict durable remission, and guide clinical development decisions