A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells

Mol Ther. 2005 Nov;12(5):933-41. doi: 10.1016/j.ymthe.2005.04.016. Epub 2005 Jun 23.


The transduction of primary T cells to express chimeric T cell receptors (cTCR) for redirected targeting of tumor cells is an attractive strategy for generating tumor-specific T cells for adoptive therapy. However, tumor cells rarely provide costimulatory signals and hence cTCRs that transmit just a CD3zeta signal can only initiate target cell killing and interferon-gamma release and fail to induce full activation. Although incorporation of a CD28 component results in IL-2 release and limited proliferation, T cell activation remains incomplete. OX40 transmits a potent and prolonged T cell activation signal and is crucial for maintaining an immunological response. We hypothesize that the CD28-OX40-CD3zeta tripartite cytoplasmic domain will provide a full complement of activation, proliferation, and survival signals for enhanced anti-tumor activity.

Publication types

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

MeSH terms

  • CD28 Antigens
  • CD3 Complex / metabolism
  • Cell Line
  • Cytokines / metabolism
  • Humans
  • Lymphocyte Activation*
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / metabolism
  • Recombinant Fusion Proteins / immunology*
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • CD28 Antigens
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Cytokines
  • Receptors, Antigen, T-Cell
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • TNFRSF4 protein, human