A major role for CD4⁺ T cells in driving cytokine release syndrome during CAR T cell therapy.

ABSTRACT: 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

SUBMITTER: Boulch M 

PROVIDER: S-EPMC10518592 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature