The tight junction protein claudin-1 - a driver of fibrosis and cell plasticity

Frontiers in Cancer Research - Lecture series

Joachim Lupberger, PhD - Director de recherche at Inserm and Tenured Scientist
Institute for Viral and Liver Disease,
Inserm U1110, University of Strasbourg, France

Claudin-1 (CLDN1) is a member of the tight junction protein family. Although the role of CLDN1 incorporated in tight junctions is well established, the function of non-junctional CLDN1 is largely unknown. In this seminar I will provide novel insight into the role of CLDN1 in disease and cancer. Using patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models we revealed that CLDN1 is a mediator of liver fibrosis. We generated a fully humanized CLDN1-specific antibody and safety studies in nonhuman primates did not reveal any serious adverse events even at high steady-state concentrations. Targeting CLDN1 reverted inflammation-induced profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. Our results provide preclinical proof of concept for CLDN1-specific monoclonal antibodies for the treatment of advanced liver fibrosis and cancer prevention. Antifibrotic effects in lung and kidney fibrosis models further indicate a role of CLDN1 as a therapeutic target for tissue fibrosis across organs. In conclusion, our work paves the way for further therapeutic exploration of CLDN1-targeting therapies for fibrotic diseases in patients.

When: Monday, March 20th, 2023, 12:00pm – 1:00pm
Where: The Meakins Amphitheatre – McIntyre Room 521