Recent advances in the prevention and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy

Adoptive immunotherapy has recently garnered widespread interests owing to the successful application of chimeric antigen receptor T cell therapy. CAR-T cells are "living drugs" that can live in patients for several years and act as an effective antitumor agent. Over the last few years, five types of CAR-T cells have been approved by Food and Drug Administration (FDA) for treatment of hematologic malignancies. Despite their impressive clinical efficacy, the current application of CAR-T cell therapy is restricted by the uncontrollable release of cytokines (cytokine release syndrome and cytokine release syndrome) due to serious treatment-related toxicities resulting from synchronous activation and rapid proliferation of CAR-T cells. CRS is the most common toxicity and its severity can range from low-grade physical symptoms to a high-grade syndrome linked with life-threatening multiple organ dysfunction. Treatment-related deaths from severe CRS have been reported, suggesting the importance of appropriate intervention. Gaining a better understanding of CRS and developing new treatments for CRS are active areas of laboratory and clinical research. Herein, we summarize the current studies on prevention and management of CRS to expand the safety and applicability of CAR-T cell therapy in various malignancies.