ArticleMolecular cancer therapeutics2013
A recombinant immunotoxin against the tumor-associated antigen mesothelin reengineered for high activity, low off-target toxicity, and reduced antigenicity.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 92 citations in OpenAlex.
- Novel PE-DT-fusion toxin enhances internalization and target-dependently restores the cytotoxicity of recombinant immunotoxins.Frontiers in pharmacology · 2026Article
- Novel perspectives on MSLN-targeted cancer therapy: from molecular mechanisms to clinical translation.Cancer biology & therapy · 2025Review
- Taming Bacterial Toxins into an Anticancer Platform.Biochemical and biophysical research communications · 2025Article
- Evaluating CAR-T cells from neurofibromatosis type 1 (NF1) patients for targeting AXL in malignant peripheral nerve sheath tumors associated with NF1.British journal of cancer · 2025Article
- Tofacitinib to prevent anti-drug antibody formation against LMB-100 immunotoxin in patients with advanced mesothelin-expressing cancers.Frontiers in oncology · 2024Article
- Novel Anti-Mesothelin Nanobodies and Recombinant Immunotoxins withMolecules and cells · 2023Article
- Enhanced cytotoxicity of aFrontiers in pharmacology · 2023Article
- GPC1-Targeted Immunotoxins Inhibit Pancreatic Tumor Growth in Mice via Depletion of Short-lived GPC1 and Downregulation of Wnt Signaling.Molecular cancer therapeutics · 2022Article
- Comparison of CD3e Antibody and CD3e-sZAP Immunotoxin Treatment in Mice Identifies sZAP as the Main Driver of Vascular Leakage.Biomedicines · 2022Article
- CD3e-immunotoxin spares CD62LFrontiers in immunology · 2022Article
- Bacteria-derived chimeric toxins as potential anticancer agents.Frontiers in oncology · 2022Review
- Targeting chemokines for acute lymphoblastic leukemia therapy.Journal of hematology & oncology · 2021Review
- An immunotoxin targeting Ebola virus glycoprotein inhibits Ebola virus production from infected cells.PloS one · 2021Article
- Review
- Expert's views and perspectives: an interview with distinguished investigator Dr. Ira Pastan at the National Cancer Institute at NIH.Antibody therapeutics · 2020Article
- Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors.Biomolecules · 2020Review
- Development of Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer: An Update.Biomolecules · 2020Review
- Immunotoxin SS1P is rapidly removed by proximal tubule cells of kidney, whose damage contributes to albumin loss in urine.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Comparison between Fractionated Dose and Single Dose of Cu-64 Trastuzumab Therapy in the NCI-N87 Gastric Cancer Mouse Model.International journal of molecular sciences · 2019Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
SS1P is a recombinant immunotoxin (RIT) engineered for the targeted elimination of malignant cells that express the tumor-associated antigen mesothelin. It is composed of an antimesothelin antibody variable fragment (Fv) linked to a cytotoxic fragment of Pseudomonas exotoxin A (PE) that includes domains II and III of native PE. The clinical use of SS1P is limited by its propensity to induce neutralizing antibodies and to cause a dose-limiting capillary leak syndrome (CLS) in patients. In this article, we describe a reengineered SS1P with improved properties that overcome these deficits. The redesign of SS1P consists of (i) removing the bulk of PE domain II (residues 251-273 and 284-394 of native PE), leaving only an 11-residue furin cleavage site, (ii) adding a Gly-Gly-Ser peptide linker after the furin cleavage site, and (iii) replacing eight highly solvent-exposed residues in the catalytic domain of PE. The new molecule, SS1-LR/GGS/8M, has cytotoxic activity comparable with SS1P on several mesothelin-expressing cell lines and remarkably improved activity on primary cells from patients with mesothelioma. In a mouse xenograft tumor model, high doses of SS1-LR/GGS/8M elicit antitumor activity superior to the activity of SS1P at its maximum-tolerated dose. In addition, SS1-LR/GGS/8M has greatly decreased ability to cause CLS in a rat model and reduced antigenicity or reactivity with antibodies to the sera of patients previously treated with SS1P.
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