biostudies-literatureFleming BDIntramural NIH HHSNational Cancer InstituteNCI NIH HHS1696-1711https://www.ebi.ac.uk/biostudies/studies/S-EPMC7069773biostudies-literatureUnknown71(5)<h4>Background and aims</h4>Treatment of hepatocellular carcinomas using our glypican-3 (GPC3)-targeting human nanobody (HN3) immunotoxins causes potent tumor regression by blocking protein synthesis and down-regulating the Wnt signaling pathway. However, immunogenicity and a short serum half-life may limit the ability of immunotoxins to transition to the clinic.<h4>Approach and results</h4>To address these concerns, we engineered HN3-based immunotoxins to contain various deimmunized Pseudomonas exotoxin (PE) domains. This included HN3-T20, which was modified to remove T-cell epitopes and contains a PE domain II truncation. We compared them to our previously reported B-cell deimmunized immunotoxin (HN3-mPE24) and our original HN3-immunotoxin with a wild-type PE domain (HN3-PE38). All of ouHepatology (Baltimore, Md.)Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention.PMC7069773Z01 BC010891ZIA BC010891Pastan IHall MDFleming BDGreten TFHo MLongerich TUrban DJfalseEngineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention.<h4>Background and aims</h4>Treatment of hepatocellular carcinomas using our glypican-3 (GPC3)-targeting human nanobody (HN3) immunotoxins causes potent tumor regression by blocking protein synthesis and down-regulating the Wnt signaling pathway. However, immunogenicity and a short serum half-life may limit the ability of immunotoxins to transition to the clinic.<h4>Approach and results</h4>To address these concerns, we engineered HN3-based immunotoxins to contain various deimmunized Pseudomonas exotoxin (PE) domains. This included HN3-T20, which was modified to remove T-cell epitopes and contains a PE domain II truncation. We compared them to our previously reported B-cell deimmunized immunotoxin (HN3-mPE24) and our original HN3-immunotoxin with a wild-type PE domain (HN3-PE38). All of ou2020-01-01T00:00:00Z2020 May2025-04-05T10:07:25.668Z2022-02-09T18:10:11.439ZS-EPMC70697733152052810.1002/hep.30949