CD3E and neoplasm: These findings are in agreement with a recent report that substitution of the ICD from alternative CD3 subunits for the ζ chain-derived domain conferred on T cells comparable antigen-specific cytotoxicity and in vivo tumor-suppressive activity.19 More importantly, CAR reconstitution with the endodomain from CD3ε yielded competent CAR-T cells with self-restrained on-membrane CAR expression, which contributed to remarkably decreased cytokine production (Supplementary Fig. 16).