A Systematic Review on the Dual Role of Interleukin-1 in CAR T-Cell Therapy: Enhancer and Mitigator

Chimeric antigen receptor (CAR) T-cell therapy is a groundbreaking approach for treating certain hematologic malignancies and solid tumors. However, its application is limited by severe toxicities, particularly cytokine release syndrome (CRS) and cell-associated neurotoxicity syndrome (ICANS), dramatically limit its broader application. IL-1 plays a crucial role in both enhancing CAR T-cell efficacy and driving these toxic effects. This review systematically examines the dual functions of IL-1, highlighting its role in promoting CAR T-cell activation and persistence while contributing to CRS and ICANS pathogenesis. Strategies to mitigate IL-1-driven toxicities, including IL-1 receptor antagonists, monoclonal antibodies, IL-1 trapping, and interference with IL-1 production, show promise in reducing adverse effects without compromising therapeutic efficacy. Understanding the complex role of IL-1 in CAR T-cell therapy may lead to optimized treatment strategies, improving safety and expanding clinical applicability. Further research is essential to refine IL-1-targeted interventions and enhance the therapeutic potential of CAR T-cell therapy.