Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response

Nat Commun. 2019 May 7;10(1):2087. doi: 10.1038/s41467-019-10097-0.


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 cells are shown to engage the signaling capacity of the entire TCR complex in an HLA-independent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD19 / immunology
  • Antigens, Neoplasm / immunology
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Mice, Inbred NOD
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Primary Cell Culture
  • Protein Domains
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Artificial / genetics
  • Receptors, Artificial / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology*
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays


  • Antigens, CD19
  • Antigens, Neoplasm
  • Receptors, Antigen, T-Cell
  • Receptors, Artificial
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies