Figure 2: Current molecular understanding and therapeutic intervention of CAR T cell-induced cytokine release syndrome and neurotoxicity.

Upon recognition of tumour antigen, the anti-tumour response activated downstream in chimeric antigen receptor (CAR) T cells leads to activation of innate immune cells owing to secretion of inflammatory cytokines like granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-1 (IL-1). This leads to a self-amplifying inflammatory activation loop in macrophages causing release of IL-1 and IL-6. Therapeutic intervention at various stages of this response can mitigate neurotoxicity and cytokine releases syndrome (CRS). Antibody therapeutics targeting GM-CSF (lenzilumab), the IL-6 receptor (tocilizumab), and the IL-1 receptor (anakinra) have been used for this purpose clinically. Tyrosine kinase inhibitor dasatinib affects T cell signaling to reduce CRS and metyrosine inhibits macrophage inflammatory activation to achieve a similar effect. IFNγ, interferon-γ; TNF, tumour necrosis factor.

This figure is copyrighted by Nature Reviews Cancer and can be found at: https://www.nature.com/articles/s41568-020-00323-z.