{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:51:17Z","timestamp":1787064677937,"version":"build-2736575974"},"reference-count":66,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R15CA198927\u201001"],"award-info":[{"award-number":["R15CA198927\u201001"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mesothelin is a protein expressed at high levels on the cell surface in a variety of cancers, with limited expression in healthy tissues. The presence of mesothelin on tumor tissue correlates with increased invasion and metastasis, and resistance to traditional chemotherapies, through mechanisms that remain poorly understood. Molecules that specifically recognize mesothelin and interrupt its contribution to tumor progression have significant potential for targeted therapy and targeted drug delivery applications. A number of mesothelin\u2010targeting therapies are in preclinical and clinical development, although none are currently approved for routine clinical use. In this work, we report the development of a mesothelin\u2010targeting protein based on the fibronectin type\u2010III non\u2010antibody protein scaffold, which offers opportunities for applications where antibodies have limitations. We engineered protein variants that bind mesothelin with high affinity and selectively initiate apoptosis in tumor cells expressing mesothelin. Interestingly, apoptosis does not occur through a caspase\u2010mediated pathway and does not require downregulation of cell\u2010surface mesothelin, suggesting a currently unknown pathway through which mesothelin contributes to cancer progression. Importantly, simultaneous treatment with mesothelin\u2010binding protein and chemotherapeutic mitomycin C had a greater cytotoxic effect on mesothelin\u2010positive cells compared to either molecule alone, underscoring the potential for combination therapy including biologics targeting mesothelin.<\/jats:p>","DOI":"10.1002\/bit.27204","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T04:19:22Z","timestamp":1571631562000},"page":"330-341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Engineered Fn3 protein has targeted therapeutic effect on mesothelin\u2010expressing cancer cells and increases tumor cell sensitivity to chemotherapy"],"prefix":"10.1002","volume":"117","author":[{"given":"Allison R.","family":"Sirois","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology Program University of Massachusetts Amherst Amherst Massachusetts"},{"name":"Picker 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