Open AccessPredictive role of endothelial cell activation in cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukaemia
Author(s) -
Hong Fei,
Shi Ming,
Cao Jiang,
Wang Ying,
Gong Yanqing,
Gao Hui,
Li Zhenyu,
Zheng Junnian,
Zeng Lingyu,
He Aili,
Xu Kailin
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17029
Subject(s) - immunology , medicine , endothelial activation , chimeric antigen receptor , cytokine , cd19 , endothelial stem cell , t cell , cell therapy , cytokine release syndrome , receptor , endothelial dysfunction , cancer research , antigen , inflammation , biology , immune system , stem cell , microbiology and biotechnology , biochemistry , in vitro
CD19‐target chimeric antigen receptor (CAR)‐T cell therapy is highly effective for relapsed/refractory (R/R) acute lymphoblastic leukaemia (ALL), but is often complicated by cytokine release syndrome (CRS), which is potentially life‐threatening. Endothelial cells are the core regulator of CRS in many infectious diseases and may also play a key role after CAR‐T cell therapy. We provided a detailed clinical, laboratory description and endothelial cell activation biomarkers in patients with CRS. Endothelial cell activation was associated with occurrence, development and severity of CRS, manifested by decreased serum angiopoietin (Ang)‐1 levels and increased levels of von Willebrand Factor (VWF), Ang‐2, Ang‐2:Ang‐1, sE‐selectin, soluble intercellular adhesion molecule (sICAM‐1) and soluble vascular cell adhesion molecule (sVCAM)‐1. Besides, the endothelial activation was correlated with the hepatic, kidney and hematopoietic dysfunction in CRS patients. After infusion of CAR‐T cells, we detected changes of endothelial activation‐related biomarkers within 36 hours in patients who subsequently developed CRS, especially severe CRS. Using top tree models, we could predict which patients would develop CRS, especially severe CRS, or identify the severity of CRS by certain biomarkers of endothelial activation. These data provide a new idea and will help identify new targets for early intervention and prevention of CRS.