A Major Role for CD4 T cells in Driving Cytokine Release Syndrome During CAR T cell Therapy

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2023 Aug 18

PMID 37595589

Authors

Morgane Boulch

Marine Cazaux

Alexis Cuffel

Mathilde Ruggiu

Vincent Allain

Beatrice Corre

Yann Loe-Mie

Benoit Hosten

Salvatore Cisternino

Sylvain Auvity

Catherine Thieblemont

Sophie Caillat-Zucman

Philippe Bousso

Affiliations

Soon will be listed here.

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 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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