T-cell killing of heterogenous tumor or viral targets with bispecific chimeric immune receptors

Cancer Gene Ther. 2000 Aug;7(8):1127-34. doi: 10.1038/sj.cgt.7700213.


We have previously described several novel chimeric immune receptors (CIRs) that redirect human T cells to kill malignant or HIV-infected cells. These CIRs comprise a cancer- or virus-specific ligand or single-chain antibody fused to the signaling domain of the T-cell receptor CD3-zeta subunit. Binding of the ligand- or antibody-based CIR to the target antigen (Ag) triggers T-cell-mediated cytolysis of the tumor- or virus-infected cell independent of target cell major histocompatibility complex class I expression. A new type of CIR was developed to mediate the lysis of cells that expressed one or more distinct viral or tumor Ags; three bispecific CIRs (BCIRs) were generated that recognized the carcinoembryonic Ag (CEA) and TAG-72 tumor Ags or, alternatively, distinct epitopes in the HIV envelope (HIVenv). T cells expressing the antitumoral Ag BCIR lysed both CEA- and TAG-72-expressing targets and did not kill Ag-negative targets or target cells expressing other members of the CEA family. Similarly, T cells expressing the anti-HIVenv BCIR lysed target cells expressing both the wild-type HIVenv and a mutant HIVenv that lacked the epitopes recognized by the monospecific CIRs. This approach permits the generation of T cells with a broader spectrum of activity capable of killing virus-infected cells and malignant cells and reduces the potential of progression of disease due to Ag loss variants.

MeSH terms

  • Amino Acid Sequence
  • Antigens / immunology
  • HIV / immunology*
  • Humans
  • Molecular Sequence Data
  • Receptors, Immunologic / immunology*
  • Recombinant Fusion Proteins / immunology*
  • T-Lymphocytes / immunology*


  • Antigens
  • Receptors, Immunologic
  • Recombinant Fusion Proteins