Posted: Friday, December 2, 2022
Monoclonal antibodies that are specific to the transmembrane protein claudin-1 may eventually prove to be effective in the treatment of intra- and extrahepatic cholangiocarcinoma, according to the preclinical results of proof-of-concept research presented during the 2022 American Association for the Study of Liver Diseases (AASLD) Annual Meeting (Abstract 202). RNA sequencing and proteomics resulted in the “robust” outcomes, which “set the stage for…clinical development” of these antibodies against a cancer that currently has unsatisfactory treatment options, wrote Thomas F. Baumert, MD, of Institut de Recherche sur Les Maladies Virales et Hépatiques, Strasbourg, France, and colleagues.
Comprehensive analyses initially revealed the strong expression of claudin-1 in cholangiocarcinoma tumor cells, revealing its potential as a therapeutic target, the authors explained. They then targeted exposed nonjunctional claudin-1 with highly specific monoclonal antibodies they developed, which resulted in significant antitumoral effects in vivo in xenograft mouse models as well as in human cholangiocarcinoma lines.
In terms of mechanistic specifics, the claudin-1 monoclonal antibodies “suppressed Notch1, Src, and Hippo-YAP signaling, which are key signal transduction pathways implicated in cholangiocarcinoma development and progression,” continued Dr. Baumert and co-investigators. In short, the antibodies markedly suppressed both the migration and invasion of cholangiocarcinoma tumor cells.
This work may be especially significant given the fact that in recent years, there has been a increase in cholangiocarcinoma incidence and mortality, the team continued. In their previous research, they had shown the claudin-1 monoclonal antibody was safe in nonhuman primates. Claudin-1 is involved in epithelial tight junctions, but it also is expressed nonjunctionally, mediating cell plasticity and signaling.
Disclosure: The study authors’ disclosure information can be found at aasldpubs.onlinelibrary.wiley.com.