CEACAM5 and neoplasm: Severe toxicity stemming from on-target off-tumor cytotoxicity was reported in several clinical trials where CAIX targeting CAR-T cells infiltrated the antigen expressing bile-ducts causing grade 2 to 4 hepatotoxicity even at the lowest used treatment doses, as well as the severe respiratory toxicity in the trial assessing CEACAM5 targeting CAR-T cells which led to trial closure (141, 148).