Immunotherapy-based targeting of MSLN + activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis

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.