The effect of dexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific single-chain antibody construct

Cancer Immunol Immunother. 2007 Oct;56(10):1551-63. doi: 10.1007/s00262-007-0298-z. Epub 2007 Feb 20.


BiTE molecules comprise a new class of bispecific single-chain antibodies redirecting previously unstimulated CD8+ and CD4+ T cells for the elimination of target cells. One example is MT103 (MEDI-538; bscCD19xCD3), a CD19-specific BiTE that can induce lysis of normal and malignant B cells at low picomolar concentrations, which is accompanied by T cell activation. Here, we explored in cell culture the impact of the glucocorticoid derivative dexamethasone on various activation parameters of human T cells in response to MT103. In case cytokine-related side effects should occur with BiTE molecules and other T cell-based approaches during cancer therapy it is important to understand whether glucocorticoids do interfere with the cytotoxic potential of T cells. We found that MT103 induced in the presence of target cells secretion by peripheral T cells of interleukin (IL)-2, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, IL-10 and IL-4 into the cell culture medium. Production of all studied cytokines was effectively reduced by dexamethasone at a concentration between 1 and 3x10(-7) M. In contrast, upregulation of activation markers CD69, CD25, CD2 and LFA-1 on both CD4+ and CD8+ T cells, and T cell proliferation were barely affected by the steroid hormone analogue. Most importantly, dexamethasone did not detectably inhibit the cytotoxic activity of MT103-activated T cells against a human B lymphoma line as investigated with lymphocytes from 12 human donors. Glucocorticoids thus qualify as a potential co-medication for therapeutic BiTE molecules and other cytotoxic T cell therapies for treatment of cancer.

MeSH terms

  • Antibodies, Bispecific / pharmacology*
  • Antigens, CD / metabolism
  • Antigens, CD19 / immunology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / drug effects
  • Dexamethasone / pharmacology*
  • Glucocorticoids / pharmacology*
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Neoplasms / immunology*
  • Neoplasms / therapy


  • Antibodies, Bispecific
  • Antigens, CD
  • Antigens, CD19
  • CD3 Complex
  • Cytokines
  • Glucocorticoids
  • Lymphocyte Function-Associated Antigen-1
  • blinatumomab
  • Dexamethasone