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CAR-T cell-induced cytokine release syndrome is rapidly alleviated by tripterygium glycosides (preprint)
researchsquare; 2022.
Preprint
in English
| PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2331958.v1
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 neglectably 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.Conclusions 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.
Full text:
Available
Collection:
Preprints
Database:
PREPRINT-RESEARCHSQUARE
Main subject:
Hematologic Neoplasms
/
Fever
/
COVID-19
Language:
English
Year:
2022
Document Type:
Preprint
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