T cells expressing CD19-specific chimeric antigen receptors (CARs) show remarkable efficacy in the treatment of B cell malignancies, but high cytokine release and underwhelming performance in solid tumors limit their wider applicability. Here, we report that T cell receptor fusion constructs (TRuC™) comprising an antibody-based binding domain fused to one of the T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens independent of HLA. Unlike CARs, TRuCs become a functional component of the TCR complex and engage the signaling capacity of the entire TCR. TRuC-T cells demonstrate potent anti-tumor efficacy in liquid and solid tumor models, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain, potentially translating into a better safety profile. Compared to CAR-T cells, TRuC-T cells traffic faster to tumors, show a favorable metabolic profile and long persistence required to prevent relapse. The first TRuC-T cells targeting mesothelin-positive tumors (TC-210) have entered phase I clinical trials.