Table 1.

Reports of life-threatening and fatal adverse events in CAR T-cell clinical trials.

Trial	Event	Reference
CAIX CAR T cells (first generation)	Grade 3 and 4 transient liver enzyme increases at 1–2 × 109 total cell dose as on-target toxicity related to CAIX expression on bile duct, preventable by pre-treatment with anti-CAIX monoclonal antibody.	Lamers et al. (2006, 2013)
CD19 CAR T cells (second generation)	Tumor lysis syndrome at 3 × 108/kg total cell dose (1.46 × 105/kg CAR T cells), resolved by day 26 after infusion. Severe cytokine-release syndrome, reversible by monoclonal antibody blockade at 1 × 108/kg cell dose (1.2 × 107/kg CAR T cells).	Porter et al. (2011), Grupp et al. (2013)
HER2/neu (ERBB2) CAR T cells (third generation)	Respiratory distress and death at 1 × 1010 total cell dose, likely due to CAR T cell localization to the lung and “cytokine storm.”	Morgan et al. (2010)
CD19 CAR T cells (second generation)	Renal failure, “sepsis-syndrome,” elevated cytokine levels and death at 1.2 × 107/kg, possibly due to a combination of sepsis, cyclophosphamide treatment and T-cell transfer.	Brentjens et al. (2010)