Abstract
Autoimmune diseases result from the immune system erroneously attacking the body’s own healthy cells, tissues, and organs, causing a broad range of chronic and often debilitating disorders. While chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative option for severe, treatment-resistant autoimmune conditions, its clinical use is limited by risks such as cytokine release syndrome and potentially life-threatening sepsis. This review highlights a strategy to enhance CAR T-cell therapy by integrating preformed anti-IgE:IgE complexes, particularly those using clone 8D6 antibody (and its humanized counterpart, UB-221). By engineering these complexes to selectively engage CD23 receptors on immune-regulatory cells, this approach aims to minimize CAR T-cell therapy toxicities. This review examines the mechanistic rationale, therapeutic implications, and future directions for combining preformed anti-IgE:IgE complexes with CAR T-cell therapy, proposing a safer, more effective pathway for treating refractory autoimmune diseases.