The transferrin receptor part I: Biology and targeting with cytotoxic antibodies for the treatment of cancer

Clin Immunol. 2006 Nov;121(2):144-58. doi: 10.1016/j.clim.2006.06.010. Epub 2006 Aug 10.

Abstract

The transferrin receptor (TfR) is a cell membrane-associated glycoprotein involved in the cellular uptake of iron and in the regulation of cell growth. Iron uptake occurs via the internalization of iron-loaded transferrin (Tf) mediated by the interaction with the TfR. In addition, the TfR may also contain other growth regulatory properties in certain normal and malignant cells. The elevated levels of TfR in malignancies, its relevance in cancer, and the extracellular accessibility of this molecule make it an excellent antigen for the treatment of cancer using antibodies. The TfR can be targeted by monoclonal antibodies specific for the extracellular domain of the receptor. In this review, we summarize advancements in the basic physiology of the TfR including structure, function, and expression. We also discuss the efficacy of targeting the TfR using cytotoxic antibodies that inhibit cell growth and/or induce apoptosis in targeted malignant cells.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Apoptosis
  • Cell Proliferation
  • Cytoplasm / metabolism
  • Humans
  • Iron / pharmacokinetics
  • K562 Cells
  • Mice
  • Models, Biological
  • Neoplasms / therapy*
  • Receptors, Transferrin / immunology
  • Receptors, Transferrin / metabolism
  • Receptors, Transferrin / physiology*
  • Transferrin / chemistry*

Substances

  • Antibodies, Monoclonal
  • Receptors, Transferrin
  • TFR2 protein, human
  • Transferrin
  • Iron