In addition, although CD28 CSD was linked with a shorter persistence and increased T-cell exhaustion compared to 4-1BB CSD constructs, an FGFR4 CAR using both CD28 HTM and CSD demonstrated significantly enhanced anti-tumor activity, leading to extended survival compared to the 4-1BB-based CARs in a more aggressive RMS559 model. This evidence concerns the gene CD28 and neoplasm.