biostudies-literatureUnknown10(1)Baeuerle PAT cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that T cell receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component of the TCR complex. TRuC-T cells kill tumor cells as potently as second-generation CAR-T cells, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor activity in both liquid and solid tumor xenograft models. In several models, TRuC-T cells are more efficacious than respective CAR-T cells. TRuC-T ceNature communications2087https://www.ebi.ac.uk/biostudies/studies/S-EPMC6504948biostudies-literatureSynthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response.PMC6504948Gierut JThorausch NPatel EMorath AHofmeister RSchamel WWDing JBaeuerle PAChoudhary RKiner OScarfo IQuinn JWei QGetts DHorton HWeiler SBaldeviano GCTavares PMaus MVKrishnamurthy JLe BfalseSynthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response.T cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that T cell receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component of the TCR complex. TRuC-T cells kill tumor cells as potently as second-generation CAR-T cells, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor activity in both liquid and solid tumor xenograft models. In several models, TRuC-T cells are more efficacious than respective CAR-T cells. TRuC-T ce2019-01-01T00:00:00Z2019 May2026-05-07T14:29:33.422Z2019-06-06T23:01:39ZS-EPMC65049483106499010.1038/s41467-019-10097-0