Optimizing the safety of chimeric antigen receptor T cell therapy — current strategies and future direction

Chimeric antigen receptor T cell (CAR-T) therapy represents a significant advancement in the treatment of hematologic malignancies, allowing for targeted recognition and elimination of tumor cells. This review summarizes current knowledge on immunoeffector cell-associated hematotoxicity (ICAHT), cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which constitute the main complications following CAR-T cell administration. Particular emphasis is placed on pharmacotherapeutic strategies reported in the literature for managing these toxicities. The review also discusses recent findings on potential biomarkers that may predict the onset of CRS and ICANS, enabling early intervention and mitigation of symptoms. Furthermore, attention is given to novel approaches described in recent studies, including the use of the CRISPR-Cas9 system for generating “off-the-shelf” CAR-T cells, editing immune checkpoint regulators, and developing dual-target or logic-gated CAR constructs to enhance tumor specificity and safety.