CAR-T cell-induced cytokine release syndrome is rapidly alleviated by Tripterygium glycosides: A case series and laboratory examination study

Abstract Background Cytokine release syndrome (CRS) is a life-threatening complication of chimeric antigen receptor T cell (CAR-T) therapy. Macrophages/monocytes are mediators of CRS. Tripterygium glycosides is an immunomodulator which could inhibit macrophages/monocytes in animal models. Methods Two patients with relapsed and refractory hematological malignancies developed CRS after receiving CAR-T therapy. They received short-term Tripterygium glycosides orally. Results Both patients showed rapid mitigation of fever with evidently decrease in elevated inflammatory cytokines within 72 hours. The patients’ monocytes diminished remarkably, while CAR-T cells were negligibly affected. Treatment of 30 ng/mL triptolide in ex vivo cultured patients’ blood for 24 hours selectively deplete over half of monocytes. Single cell RNA sequencing suggested selective depletion of CD14+CD16+ monocytes with decreased pro-inflammatory cytokines. Conclusion The low-cost and orally available Tripterygium glycosides could be a promising alternative for CAR-T induced CRS, as well as other diseases complicated with CRS, e.g., coronavirus disease 2019.