TY - JOUR T1 - Anti-claudin antibodies as a concept for development of claudin-directed drugs JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.118.252361 SP - jpet.118.252361 AU - Yosuke Hashimoto AU - Yoshiaki Okada AU - Keisuke Shirakura AU - Keisuke Tachibana AU - Makoto Sawada AU - Kiyohito Yagi AU - Takefumi Doi AU - Masuo Kondoh Y1 - 2018/01/01 UR - http://jpet.aspetjournals.org/content/early/2018/12/07/jpet.118.252361.abstract N2 - Claudin (CLDN) proteins, a tetra-transmembrane family containing over 20 members, have been identified as a key structural and functional component of intercellular seals, tight junctions (TJs). CLDNs are involved in the barrier and fence functions of TJs. Loosening the TJ barrier is one strategy for increasing drug absorption and delivery to the brain. Due to aberrant CLDN expression, the TJ fence function is frequently dysregulated in carcinogenesis. In addition, CLDN-1 is a co-receptor for the hepatitis C virus. Together these characteristics indicate CLDNs as promising targets for drug development, and CLDN binders are potential candidates for delivering drugs, treating cancer, and preventing viral infection. Before 2008, a receptor-binding fragment of Clostridium perfringens enterotoxin was the only CLDN binder available. Since then, several challenges regarding the generation of monoclonal antibodies against CLDNs have been surmounted, leading to breakthroughs in CLDN-targeted drug development. Here, we provide an overview of the recent progress in technology using created CLDN binders--anti-CLDN monoclonal antibodies. ER -