Tonic signal triggered by CARs in the absence of specific antigens impedes the tumoricidal persistence of CAR-T cells.23 We first monitored the tonic/auto-activation of a CAR-modulated human T cell lymphoma cell line, Jurkat, via flow-cytometric detection of CD69 expression (Fig. 2a).24 The levels of CD69 in cells transduced to express ri-CARs were remarkably lower than cells expressing the conventional CAR, which was independent of tumor antigens recognized by CARs (Fig. 2b; Supplementary Fig. 2a, b). Here, CD69 is linked to neoplasm.