{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:39:39Z","timestamp":1790703579365,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,6,28]],"date-time":"2020-06-28T00:00:00Z","timestamp":1593302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA BC 011652"],"award-info":[{"award-number":["ZIA BC 011652"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Mesothelin (MSLN) is a cell surface glycoprotein normally expressed only on serosal surfaces, and not found in the parenchyma of vital organs. Many solid tumors also express MSLN, including mesothelioma and pancreatic adenocarcinoma. Due to this favorable expression profile, MSLN represents a viable target for directed anti-neoplastic therapies, such as recombinant immunotoxins (iToxs). Pre-clinical testing of MSLN-targeted iTox\u2019s has yielded a strong body of evidence for activity against a number of solid tumors. This has led to multiple clinical trials, testing the safety and efficacy of the clinical leads SS1P and LMB-100. While promising clinical results have been observed, neutralizing anti-drug antibody (ADA) formation presents a major challenge to overcome in the therapeutic development process. Additionally, on-target, off-tumor toxicity from serositis and non-specific capillary leak syndrome (CLS) also limits the dose, and therefore, impact anti-tumor activity. This review summarizes existing pre-clinical and clinical data on MSLN-targeted iTox\u2019s. In addition, we address the potential future directions of research to enhance the activity of these anti-tumor agents.<\/jats:p>","DOI":"10.3390\/biom10070973","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T09:36:04Z","timestamp":1593509764000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-4636","authenticated-orcid":false,"given":"Brendan L.","family":"Hagerty","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA"},{"name":"Surgical Oncology Program, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume J.","family":"Pegna","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA"},{"name":"Medical Oncology Service, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Hsien","family":"Tai","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1661-0957","authenticated-orcid":false,"given":"Christine","family":"Alewine","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1073\/pnas.93.1.136","article-title":"Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesothiomas, and ovarian cancers","volume":"93","author":"Chang","year":"1996","journal-title":"Proc. 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