Immunotherapy-based targeting of MSLN <sup>+</sup> activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis
Takahiro Nishio, Yukinori Koyama, Xiao Liu, Sara Brin Rosenthal, Gen Yamamoto, Hiroaki Fuji, Jacopo Baglieri, Na Li, Laura Brenner, Keiko Iwaisako, Kojiro Taura, James S. Hagood, Nicholas F. LaRusso, Tapan K. Bera, Ira Pastan, David A. Brenner, Tatiana Kisseleva
Abstract
Significance Mesothelin (Msln) expression is increased in tissue fibroblasts of damaged liver and other organs and Msln is a common mediator of liver, lung, and kidney fibrosis. We show that anti-Msln immunotoxins kill the Msln-expressing fibroblasts and reduce collagen type I deposition in fibrotic liver, indicating that agents that specifically kill Msln-expressing cells should be a useful treatment for cholestatic fibrosis. Targeting of Msln + fibroblasts by anti-Msln immunoconjugates may become a strategy for the treatment of parenchymal organ fibrosis.