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. 2019 Dec 17;17(3):147–167. doi: 10.1038/s41571-019-0297-y

Fig. 2. Overcoming systemic cytokine toxicities of CAR T cells.

Fig. 2

The activation and rapid expansion of chimeric antigen receptor (CAR) T cells in patients treated with these agents is associated with high systemic levels of cytokines. To counter this effect in the event of systemic cytokine-related toxicities, researchers are engineering methods to control CAR expression or activity. A | CAR T cells with on/off switches predicated on small-molecule adapter ligands (a), CAR subunit-dimerizing agents (b), inhibitors of signalling downstream of the CAR (c), or protease inhibitors used to control CAR protein expression (d). B | Suicide gene systems that enable elimination of CAR T cells via induction of apoptosis (a) or antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) (b). C | CAR T cells engendered with the intrinsic ability to secrete factors that neutralize relevant cytokines. FcR, fragment crystallizable region receptor; GM-CSF, granulocyte–macrophage colony-stimulating factor; iCasp9, inducible caspase 9; IL-1R, IL-1 receptor; IL-1Ra, IL-1 receptor antagonist; mAb, monoclonal antibody; NK, natural killer; scFv, single-chain Fv; SMASh-CAR, small molecule-assisted shutoff chimeric antigen receptor.