Fig. 3. Schematic representation of current and potential therapeutic interventions for CRS.

Blockade of the IL-6 receptor (IL-6R; using the monoclonal antibody tocilizumab) has shown clinical benefit in patients with cytokine release syndrome (CRS)^4,6,29,33. In vivo and in vitro models have proposed novel therapeutic interventions for CRS that directly target pro-inflammatory cytokines — such as IL-1 (the IL-1 receptor antagonist anakinra)^{29,33,110,116}, tumour necrosis factor (TNF; adalimumab or etanercept)⁵² and granulocyte–macrophage colony-stimulating factor (GM-CSF; lenzilumab)^48,50 — or other pro-inflammatory mediators such as catecholamines (for example metirosine, which inhibits catecholamine synthesis)⁶⁰. Furthermore, kinase inhibitors such as dasatinib can inhibit chimeric antigen receptor (CAR) T cell functionality, with subsequent reduction in effector cytokine secretion¹⁰⁸. Other broad-spectrum small-molecule inhibitors, such as ruxolitinib and ibrutinib (not shown here), that can broadly inhibit cytokine signalling and cytokine production across multiple cell types have been proposed for use in CRS.