Anti-tumor activity of human T cells expressing the CC49-zeta chimeric immune receptor

Hum Gene Ther. 1999 Jan 20;10(2):165-73. doi: 10.1089/10430349950018968.


A chimeric immune receptor consisting of an extracellular antigen-binding domain derived from the CC49 humanized single-chain antibody, linked to the CD3zeta signaling domain of the T cell receptor, was generated (CC49-zeta). This receptor binds to TAG-72, a mucin antigen expressed by most human adenocarcinomas. CC49-zeta was expressed in CD4+ and CD8+ T cells and induced cytokine production on stimulation. Human T cells expressing CC49-zeta recognized and killed tumor cell lines and primary tumor cells expressing TAG-72. CC49-zeta T cells did not mediate bystander killing of TAG-72-negative cells. In addition, CC49-zeta T cells not only killed FasL-positive tumor cells in vitro and in vivo, but also survived in their presence, and were immunoprotective in intraperitoneal and subcutaneous murine tumor xenograft models with TAG-72-positive human tumor cells. Finally, receptor-positive T cells were still effective in killing TAG-72-positive targets in the presence of physiological levels of soluble TAG-72, and did not induce killing of TAG-72-negative cells under the same conditions. This approach is being currently being utilized in a phase I clinical trial for the treatment of colon cancer.

MeSH terms

  • Animals
  • Antibodies, Neoplasm / genetics
  • Antibodies, Neoplasm / immunology*
  • Antigens, Neoplasm / immunology
  • Cell Division / immunology
  • Fas Ligand Protein
  • Glycoproteins / immunology
  • Humans
  • Lymphocytes, Tumor-Infiltrating / cytology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Receptors, Immunologic / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*


  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • B72.3 antibody
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Glycoproteins
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • tumor-associated antigen 72