On November 2, 2022 Alentis Therapeutics ("Alentis" or "the Company"), the biotechnology company developing breakthrough treatments for organ fibrosis and fibrotic-associated cancers, reported that Scientific Founder Professor Thomas Baumert’s team has published an article on the role of Claudin-1 (CLDN1) in the treatment of hepatocellular carcinoma (HCC) The Journal of Hepatology (Press release, Alentis Therapeutics, NOV 2, 2022, View Source [SID1234622818]).
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Despite new treatment approvals, treatment response and prognosis of patients with advanced HCC remain poor. CLDN1 is a membrane protein expressed not only at tight junctions but also non-junctionally such as the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored.
Using humanized monoclonal antibodies (mAbs) targeting specifically the extracellular loop of human non-junctional CLDN1 and a large series of patient-derived cell-based and animal model systems, the study investigated the role of CLDN1 as a therapeutic target for HCC.
The study found that mAbs targeting CLDN1 inhibit tumor growth in patient-derived ex vivo and in vivo models by modulating signaling, cell stemness and the tumor immune microenvironment. The results provide clear evidence of the efficiency of targeting CLDN1 for HCC and paves the way for the development of novel therapeutic interventions with CLDN1 mAbs, aimed at improving the limited efficacy of current therapies.
Moreover, given the differentiated mechanism of action, the identification of CLDN1 as a novel therapeutic target for HCC provides an opportunity to break the plateau of limited treatment response, especially in advanced HCC.
Professor Thomas Baumert commented: "Hepatocellular carcinoma (HCC) is a leading cause of cancer worldwide with rising incidence and long-term survival rates are poor. These data unravel a previously undiscovered functional role of CLDN1 in HCC signaling and microenvironment and provide compelling preclinical evidence on CLDN1 as a target for drug development using monoclonal antibodies."
Roberto Iacone, CEO at Alentis Therapeutics, added: "The role of CLDN1 in cancer has long been established and these data provide robust pre-clinical proof-of-concept for CLDN1 mAbs as potential first in-class compounds for hepatocellular carcinoma. We look forward to capitalizing on this exciting data and progressing ALE.C04, our development programme targeting CLDN1 for fibrotic-associated cancers, into the clinic."
This study was led by Prof. Thomas Baumert at Inserm and the University of Strasbourg and conducted as a collaboration between Inserm, University of Strasbourg, Alentis Therapeutics, German Cancer Research Center, University of Texas Southwestern Medical Center Dallas, Massachusetts General Hospital Cancer Center and Harvard Medical School.