In this way, incorporation of the oxygen-sensitive domain of HIF-1α oxygen-dependent degradation (ODD) into the CAR scaffold, termed HIF-CAR (181), HiCAR (182), and HypoxiCAR (183), led to sub-optimal CAR expression in the normoxic setting owing to the hydroxylation and degradation of the CAR as oxygen became available, and on the other hand, high expression of the CAR in the hypoxic condition, enabling CAR T-cells to induce cytotoxic effects on tumor cells specifically. Here, HIF1A is linked to neoplasm.