Targeting cells in motion: migrating toward improved therapies

Eur J Immunol. 2013 Jun;43(6):1430-5. doi: 10.1002/eji.201243183. Epub 2013 May 13.

Abstract

The development of clinical therapeutics that interfere with the migration of leukocytes has revolutionized the treatment of multiple sclerosis and holds great promise for the treatment of a wide range of inflammatory diseases. As the molecules essential for the multi-step adhesion cascade that mediates cellular migration have been elucidated, the number of potential targets available to modulate leukocyte trafficking has increased exponentially. In this Viewpoint, we briefly review our current understanding of these mole-cular targets and how these targets vary by tissue and leukocyte subset with emphasis on T cells. We then describe the two currently approved therapeutics that target cell migration, natalizumab and fingolimod, and discuss how an improved understanding of their function could pave the way for the development of safer and more efficacious therapies for inflammatory and autoimmune diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cell Adhesion / drug effects
  • Cell Migration Inhibition
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppression Therapy
  • Immunotherapy / trends
  • Integrin alpha4 / immunology
  • Molecular Targeted Therapy
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Natalizumab
  • Propylene Glycols / pharmacology
  • Propylene Glycols / therapeutic use*
  • Signal Transduction / drug effects
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Sphingosine / therapeutic use
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Natalizumab
  • Propylene Glycols
  • Integrin alpha4
  • Fingolimod Hydrochloride
  • Sphingosine