Claudin-targeted drug development using anti-claudin monoclonal antibodies to treat hepatitis and cancer

Ann N Y Acad Sci. 2017 Jun;1397(1):5-16. doi: 10.1111/nyas.13337. Epub 2017 Apr 17.

Abstract

The 27-member family of tetraspan membrane proteins known as claudins (CLDNs) is a major component of tight junctions. A series of studies elucidating the relationship between CLDNs and various pathological conditions has provided new insights into drug development. For instance, CLDN-1 may be a potent target for epidermal absorption of drugs and for treating hepatitis C virus (HCV) infection. CLDN-4 may be a target for treating cancer. Because CLDNs are also expressed in various normal tissues, safety and efficacy evaluations are critical for translational research. We previously developed several anti-CLDN antibodies and have established proof of concept for CLDN-targeted drug development using these reagents. Here, we provide an overview of CLDN-1 as a target for improving epidermal drug absorption and preventing HCV infection and of CLDN-4 as a target for anticancer therapeutics.

Keywords: cancer; claudin; epidermal absorption; hepatitis C virus; monoclonal antibody.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Claudin-1 / immunology
  • Claudin-1 / metabolism*
  • Claudin-4 / immunology
  • Claudin-4 / metabolism*
  • Epidermis / metabolism
  • Hepacivirus / drug effects*
  • Hepacivirus / physiology
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Neoplasms / drug therapy*
  • Tight Junctions / metabolism

Substances

  • Antibodies, Monoclonal
  • Claudin-1
  • Claudin-4