Transient injury-dependent up-regulation of CD105 and its specific targeting with an anti-vascular anti-mouse endoglin-nigrin b immunotoxin

Med Chem. 2012 Nov;8(6):996-1002. doi: 10.2174/1573406411208060996.

Abstract

Endoglin (CD105), a cell-surface co-receptor for transforming growth factor-beta (TGF-β) superfamily members, is over-expressed in tumor neovasculature and can be targeted with anti-endoglin antibodies, thus becoming an important tool for anti-tumoral therapy. Injury of the mouse tail induced the transient expression of endoglin, this peaking at three days after injury and disappearing six days later. An immunotoxin containing the anti-mouse endoglin rat monoclonal antibody MJ7/18 and the non-toxic ribosome-inactivating protein nigrin b (Ngb) was found to be very active in targeting mouse endoglin in the L929 fibroblast cell line (IC(50) of 4 x 10(-11) M). At that concentration, the immunotoxin lacked unspecific activity. Upon induction of endoglin after injury, the MJ7-Ngb immunotoxin strongly attacked and deranged the injured tail, inducing tissue damage. Such effects were dependent on the age of the animals and were evident in six-week-old mice, but not in eight-month-old mice. Our results indicate that endoglin is up-regulated in newly formed vessels upon injury and can be targeted by the MJ7-Ngb immunotoxin; thus, it could be a useful tool for tumor ablation research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Cell Line
  • Endoglin
  • Humans
  • Immunomodulation / drug effects
  • Immunotoxins / immunology
  • Immunotoxins / toxicity*
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Plant Proteins / immunology*
  • Rabbits
  • Ribosome Inactivating Proteins / immunology*
  • Tail / blood supply*
  • Tail / injuries*
  • Time Factors
  • Up-Regulation / drug effects*
  • Veins / drug effects*

Substances

  • Antibodies, Monoclonal
  • Endoglin
  • Eng protein, mouse
  • Immunotoxins
  • Intracellular Signaling Peptides and Proteins
  • Plant Proteins
  • nigrin b protein, Sambucus nigra
  • Ribosome Inactivating Proteins