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Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors
Open AccessReview

Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors

Laboratory of Molecular Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA
Surgical Oncology Program, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA
Medical Oncology Service, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(7), 973;
Received: 31 May 2020 / Revised: 24 June 2020 / Accepted: 26 June 2020 / Published: 28 June 2020
(This article belongs to the Special Issue Immunotoxins: From Design to Clinical Application)
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’s 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’s. In addition, we address the potential future directions of research to enhance the activity of these anti-tumor agents. View Full-Text
Keywords: immunotoxin; mesothelin; mesothelioma; pancreatic adenocarcinoma immunotoxin; mesothelin; mesothelioma; pancreatic adenocarcinoma
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Hagerty, B.L.; Pegna, G.J.; Xu, J.; Tai, C.-H.; Alewine, C. Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors. Biomolecules 2020, 10, 973.

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