Computational modeling and experimental validation of the interaction between tumor biomarker mesothelin and an engineered targeting protein with therapeutic activity.

ABSTRACT: Mesothelin (MSLN) is a cell surface glycoprotein overexpressed in many solid tumors, which is known to interact with cancer antigen CA125/MUC16, promoting cancer cell adhesion and metastasis. MSLN has been used as a target of multiple antibody-based therapeutic strategies, but their efficacy remains limited, potentially due to inherent pharmacokinetics conferred by the structure of antibodies (~150 kDa). To provide an alternative targeting molecule, we engineered a small scaffold protein derived from the tenth domain of human fibronectin type III (Fn3, 12.8 kDa) to bind MSLN with nanomolar affinity as a theranostic agent for MSLN-positive cancers. In this study, we explored the Fn3-MSLN interaction site through computational modeling and experimentally validated the model through domain-le

SUBMITTER: Piccardi M 

PROVIDER: S-EPMC12355969 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature