Engager T cells: a new class of antigen-specific T cells that redirect bystander T cells

Mol Ther. 2015 Jan;23(1):171-8. doi: 10.1038/mt.2014.156. Epub 2014 Aug 21.


Adoptive immunotherapy with antigen-specific T cells has shown promise for the treatment of malignancies. However, infused T cells are unable to redirect resident T cells, limiting potential benefit. While the infusion of bispecific T-cell engagers can redirect resident T cells to tumors, these molecules have a short half-life, and do not self amplify. To overcome these limitations, we generated T cells expressing a secretable T-cell engager specific for CD3 and EphA2, an antigen expressed on a broad range of human tumors (EphA2-ENG T cells). EphA2-ENG T cells were activated and recognized tumor cells in an antigen-dependent manner, redirected bystander T cells to tumor cells, and had potent antitumor activity in glioma and lung cancer severe combined immunodeficiency (SCID) xenograft models associated with a significant survival benefit. This new class of tumor-specific T cells, with the unique ability to redirect bystander T cells, may be a promising alternative to current immunotherapies for cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Bystander Effect / immunology
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • Cell Line, Tumor
  • Gene Expression
  • Genetic Vectors
  • Glioma / genetics
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, SCID
  • Receptor, EphA2 / genetics
  • Receptor, EphA2 / immunology
  • Retroviridae / genetics
  • Survival Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation
  • Xenograft Model Antitumor Assays


  • Antigens, Neoplasm
  • CD3 Complex
  • Receptor, EphA2