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- W2799773035 endingPage "e0197029" @default.
- W2799773035 startingPage "e0197029" @default.
- W2799773035 abstract "Mesothelin is a cell surface protein that is overexpressed in numerous cancers, including breast, ovarian, lung, liver, and pancreatic tumors. Aberrant expression of mesothelin has been shown to promote tumor progression and metastasis through interaction with established tumor biomarker CA125. Therefore, molecules that specifically bind to mesothelin have potential therapeutic and diagnostic applications. However, no mesothelin-targeting molecules are currently approved for routine clinical use. While antibodies that target mesothelin are in development, some clinical applications may require a targeting molecule with an alternative protein fold. For example, non-antibody proteins are more suitable for molecular imaging and may facilitate diverse chemical conjugation strategies to create drug delivery complexes. In this work, we engineered variants of the fibronectin type III domain (Fn3) non-antibody protein scaffold to bind to mesothelin with high affinity, using directed evolution and yeast surface display. Lead engineered Fn3 variants were solubly produced and purified from bacterial culture at high yield. Upon specific binding to mesothelin on human cancer cell lines, the engineered Fn3 proteins internalized and co-localized to early endosomes. To our knowledge, this is the first report of non-antibody proteins engineered to bind mesothelin. The results validate that non-antibody proteins can be engineered to bind to tumor biomarker mesothelin, and encourage the continued development of engineered variants for applications such as targeted diagnostics and therapeutics." @default.
- W2799773035 created "2018-05-17" @default.
- W2799773035 creator A5006254054 @default.
- W2799773035 creator A5016892316 @default.
- W2799773035 creator A5048336476 @default.
- W2799773035 creator A5049207024 @default.
- W2799773035 creator A5053379412 @default.
- W2799773035 date "2018-05-08" @default.
- W2799773035 modified "2023-09-26" @default.
- W2799773035 title "Fn3 proteins engineered to recognize tumor biomarker mesothelin internalize upon binding" @default.
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