Together with our observation that this L1CAM-specific CAR subgroup showed significantly higher in vitro cytotoxicity compared to L1CAM-SS-CD28/ζ CAR T cells, we hypothesize that antigen-driven overactivation after repeated antigen encounter is accountable for the reduced in vivo survival and anti-tumor activity of L1CAM-LS-CD28/ζ CAR T cells. Here, CD28 is linked to neoplasm.