The toxicity of cell therapy: Mechanism, manifestations, and challenges

Abstract Adoptive cell therapy (ACT), including tumor‐infiltrating lymphocytes (TILs), T cell receptor engineered T cell (TCR‐T), and chimeric antigen receptor engineered T cell (CAR‐T), has shown significant clinical benefits for cancer treatment. However, all of these ACT therapies are associated with toxicities from mild to life threatening in clinic. Common ACT‐related toxicities include cytokine release syndrome (CRS) resulting from immune activation, neurological toxicity, on‐target/off tumor or off‐target toxicities, and toxicities associated with lymphodepletion preconditioning and high does IL‐2 administration. This review summarizes clinical manifestations of adverse events associated with ACT treatment and discusses the underlying pathological mechanisms. Moreover, challenges and opportunities of managing ACT‐related toxicities have been discussed to give an indication of how to improve the safety of ACT treatment without dampening the therapeutic effect.