It is noteworthy that in studies targeting both CLDN18.2 and GD-2, the authors utilized a 4-1BB co-stimulatory domain within the CAR structure, which is known to enhance persistence in hematological malignancies [104] but also establishes a higher activation threshold relative to CAR-T cells incorporating CD28-based co-stimulation [105]. This evidence concerns the gene CD28 and hematologic disorder.