A TCR-based Chimeric Antigen Receptor

Sci Rep. 2017 Sep 6;7(1):10713. doi: 10.1038/s41598-017-11126-y.


Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells. Hence, an introduced therapeutic TCR will compete with the endogenous TCR for the signalling proteins and carries the potential risk of mixed dimer formation giving rise to a new TCR with unpredictable specificity. We have fused a soluble TCR construct to a CAR-signalling tail and named the final product TCR-CAR. We here show that, if expressed, the TCR-CAR conserved the specificity and the functionality of the original TCR. In addition, we demonstrate that TCR-CAR redirection was not restricted to T cells. Indeed, after transduction, the NK cell line NK-92 became TCR positive and reacted against pMHC target. This opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Flow Cytometry
  • Gene Expression
  • Gene Order
  • Genetic Vectors / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunotherapy, Adoptive
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Protein Interaction Domains and Motifs / genetics
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Chimeric Antigen / chemistry
  • Receptors, Chimeric Antigen / genetics*
  • Receptors, Chimeric Antigen / metabolism*
  • Recombinant Fusion Proteins
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transduction, Genetic


  • Cytokines
  • Histocompatibility Antigens Class I
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • Recombinant Fusion Proteins