Figure 1.

Potential mechanisms of toxicity mediated by infused chimeric antigen receptor (CAR)⁺ T cells. Cytokine-induced toxicity describes damage mediated by T-cell activation and release of inflammatory cytokines, as exhibited in clinical trials with CD19-specific CAR⁺ T cells. Anaphylactic response (anaphylaxis) describes development of an IgE-mediated immune response to foreign CAR moieties that degranulates mast cells. On-target, off-tissue toxicity describes CAR⁺ T-cell recognition of tumor-associated antigens (TAAs) expressed on normal tissue(s).