嵌合抗原受体
细胞因子释放综合征
CD19
CD8型
免疫学
T细胞
细胞疗法
医学
细胞因子
免疫疗法
汽车T细胞治疗
细胞
癌症研究
抗原
生物
免疫系统
遗传学
作者
Morgane Boulch,Marine Cazaux,Alexis Cuffel,Mathilde Ruggiu,Vincent Allain,Béatrice Corre,Yann Loe-Mie,Benoît Hosten,Salvatore Cisternino,Sylvain Auvity,Catherine Thiéblemont,Sophie Caillat‐Zucman,Philippe Bousso
标识
DOI:10.1016/j.xcrm.2023.101161
摘要
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy represents a breakthrough for the treatment of B cell malignancies. Yet, it can lead to severe adverse events, including cytokine release syndrome (CRS), which may require urgent clinical management. Whether interpatient variability in CAR T cell subsets contributes to CRS is unclear. Here, we show that CD4+ CAR T cells are the main drivers of CRS. Using an immunocompetent model of anti-CD19 CAR T cell therapy, we report that CD4+, but not CD8+, CAR T cells elicit physiological CRS-like manifestations associated with the release of inflammatory cytokines. In CAR T cell-treated patients, CRS occurrence and severity are significantly associated with high absolute values of CD4+ CAR T cells in the blood. CRS in mice occurs independently of CAR T cell-derived interferon γ (IFN-γ) but requires elevated tumor burden. Thus, adjusting the CD4:CD8 CAR T cell ratio to patient tumor load may help mitigate CAR T cell-associated toxicities.
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