As reported, third-generation EpCAM CAR-T cells were generated to identify the specificity of EpCAM to CRC cells and models, demonstrated lytic cytotoxicity to target cells and secreted cytotoxic cytokines including tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) in an EpCAM-dependent manner. The gene discussed is EPCAM; the disease is colorectal carcinoma.