Characterization and receptor specific toxicity of two diphtheria toxin-related interleukin-3 fusion proteins DAB389-mIL-3 and DAB389-(Gly4Ser)2-mIL-3

FEBS Lett. 1997 Apr 7;406(1-2):157-61. doi: 10.1016/s0014-5793(97)00243-3.


We have constructed two fusion proteins, DAB389-mIL-3 and DAB389-(Gly4Ser)2-mIL-3, in which the receptor-binding domain of diphtheria toxin is replaced by mouse interleukin-3 (IL-3). Cytotoxic activity of the fusion toxins was observed on three out of six cell lines assayed. This toxicity was mediated through binding to the IL-3 receptor as it was inhibited in a dose-dependent manner with murine IL-3 or anti-IL-3 neutralizing antibodies. DAB389-(Gly4Ser)2-mIL-3 was up to 5 times more toxic than DAB389-mIL-3, depending on the cell line (0.8 x 10(-10) M < IC50 < 3 x 10(-10) M). These proteins can be used for the detection of IL-3 receptors on mouse cells and should allow for the selective elimination of IL-3 receptor-positive pluripotent hematopoietic stem cells prior to bone marrow transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Diphtheria Toxin / chemistry*
  • Diphtheria Toxin / metabolism
  • Diphtheria Toxin / toxicity
  • Interleukin-2 / chemistry*
  • Interleukin-2 / metabolism
  • Interleukin-2 / toxicity
  • Interleukin-3 / chemistry*
  • Interleukin-3 / metabolism
  • Interleukin-3 / toxicity
  • Mice
  • Protein Folding
  • Receptors, Interleukin-3 / drug effects*
  • Receptors, Interleukin-3 / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / toxicity


  • DAB(389)-(Gly(4)-Ser)2-interleukin 3
  • Diphtheria Toxin
  • Interleukin-2
  • Interleukin-3
  • Receptors, Interleukin-3
  • Recombinant Fusion Proteins
  • denileukin diftitox