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

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.