Next-generation immune cell engagers for B cell depletion in autoimmune diseases.

Early clinical reports of CD19- and B cell maturation antigen-directed immune cell engagers show sustained improvements in several systemic autoimmune diseases.

• Why it matters: Deep B cell depletion is crucial for treating autoimmune diseases, but current challenges include disease-specific B cell heterogeneity, pharmacokinetic issues, and effector-cell dysfunction, limiting therapy effectiveness.
• What they did: The authors review principles of ICE development for autoimmune diseases, focusing on target selection, engager architecture, effector-cell recruitment, and safety, and explore emerging strategies like CD8-biased T cell engagement and natural killer cell recruitment.
• The result: These advances suggest ICEs could become off-the-shelf alternatives to CAR T cell therapies, enabling sustained immune reprogramming and improved treatment outcomes for refractory autoimmune diseases.