T cell targeting of TAG72+ tumor cells by a chimeric receptor with antibody-like specificity for a carbohydrate epitope

Gastroenterology. 1997 Oct;113(4):1163-70. doi: 10.1053/gast.1997.v113.pm9322511.


Background & aims: Chimeric receptors with specificity for defined tumor antigens are valuable tools for targeting cytolytic T cells specifically to tumor cells. The aim of this study, for the situation of gastrointestinal cancer, was to investigate the generation of a chimeric T cell receptor that specifically binds the tumor antigen TAG72 (CA72-4) and transmits a signal for cellular activation.

Methods: A single-chain antibody (scFv) was derived from the monoclonal anti-TAG72 antibody B72.3 by phage display techniques (B72.3-scFv) and fused to the signaling unit of the Fc epsilon-RI receptor gamma chain, resulting in a chimeric signaling receptor, B72.3-scFv-gamma.

Results: The B72.3-scFv and the chimeric B72.3-scFv-gamma receptor bound specifically to the TAG72 antigen. After transfection, T cells expressing the chimeric B72.3-scFv-gamma specifically recognized TAG72 positive cells. Cross-linking of the chimeric receptor with antigen resulted in interleukin 2 release and cytolytic activity against TAG72 positive tumor cells in vitro.

Conclusions: T cells equipped with the chimeric anti-TAG72 receptor can be specifically activated to target and lyse TAG72 positive gastrointestinal tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Cell Line
  • Cytotoxicity, Immunologic*
  • Glycoproteins / immunology*
  • Glycoproteins / metabolism
  • Humans
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation
  • Mice
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, IgE / biosynthesis
  • Receptors, IgE / immunology
  • Receptors, IgG / biosynthesis
  • Receptors, IgG / immunology
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology*
  • Transfection


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Glycoproteins
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Receptors, IgE
  • Receptors, IgG
  • Recombinant Fusion Proteins
  • tumor-associated antigen 72