CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program

Monoclon Antib Immunodiagn Immunother. 2019 Apr;38(2):60-69. doi: 10.1089/mab.2018.0042.


CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4+ effector memory T cells (TEMs) in humans with unwanted serious adverse effects. It is well known that distinct metabolic programs determine the fate and responses of immune cells. In this study, we show that human CD4+ TEMs stimulated with CD28SA adopt a metabolic program similar to those of tumor cells with enhanced glucose utilization, lipid biosynthesis, and proliferation in hypoxic conditions. Identification of metabolic profiles underlying hyperactive T cell activation would provide a platform to test safety of immunostimulatory antibodies.

Keywords: CD28 superagonist; CD4 effector memory T cells; glycolysis; lipogenesis; oxidative phosphorylation.

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Antibodies, Monoclonal / immunology
  • CD28 Antigens / immunology*
  • CD28 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Glucose / metabolism
  • Glycolysis / immunology*
  • Humans
  • Immunologic Memory
  • Lipogenesis / immunology*
  • Lymphocyte Activation / immunology*
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Kinases / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • CD28 Antigens
  • Acetyl Coenzyme A
  • Protein Kinases
  • ATP-citrate lyase kinase
  • Glucose