ArticleProceedings of the National Academy of Sciences of the United States of America2020
Immunotoxin SS1P is rapidly removed by proximal tubule cells of kidney, whose damage contributes to albumin loss in urine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Mesothelin-Binding Peptide Inhibits Cell Migration and Enables Targeted Delivery of a Mitochondrial-Membrane-Damaging Peptide to Pancreatic Tumors.Biomaterials research · 2026Article
- Future theranostic strategies: emerging ovarian cancer biomarkers to bridge the gap between diagnosis and treatment.Frontiers in drug delivery · 2024Review
- Systemic immune changes accompany combination treatment with immunotoxin LMB-100 and nab-paclitaxel.Cancer medicine · 2023Article
- Expanding the Therapeutic Window of EGFR-Targeted PE24 Immunotoxin for EGFR-Overexpressing Cancers by Tailoring the EGFR Binding Affinity.International journal of molecular sciences · 2022Article
- Podocytes are lost from glomeruli before completing apoptosis.American journal of physiology. Renal physiology · 2022Article
- Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective.Antibody therapeutics · 2022Review
- Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin.International journal of molecular sciences · 2022Article
- The Indiana O'Brien Center for Advanced Renal Microscopic Analysis.American journal of physiology. Renal physiology · 2021Review
- IgG-Engineered Protective Antigen for Cytosolic Delivery of Proteins into Cancer Cells.ACS central science · 2021Article
- Mechanism of how carbamylation reduces albumin binding to FcRn contributing to increased vascular clearance.American journal of physiology. Renal physiology · 2021Article
- Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors.Biomolecules · 2020Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Recombinant immunotoxins (RITs) are chimeric proteins composed of an Fv and a protein toxin being developed for cancer treatment. The Fv brings the toxin to the cancer cell, but most of the RITs do not reach the tumor and are removed by other organs. To identify cells responsible for RIT removal, and the pathway by which RITs reach these cells, we studied SS1P, a 63-kDa RIT that targets mesothelin-expressing tumors and has a short serum half-life. The major organs that remove RIT were identified by live mouse imaging of RIT labeled with FNIR-Z-759. Cells responsible for SS1P removal were identified by immunohistochemistry and intravital two-photon microscopy of kidneys of rats. The primary organ of SS1P removal is kidney followed by liver. In the kidney, SS1P passes through the glomerulus, is taken up by proximal tubular cells, and transferred to lysosomes. In the liver, macrophages are involved in removal. The short half-life of SS1P is due to its very rapid filtration by the kidney followed by degradation in proximal tubular cells of the kidney. In mice treated with SS1P, proximal tubular cells are damaged and albumin in the urine is increased. SS1P uptake by kidney is reduced by coadministration of l-lysine. Our data suggests that l-lysine administration to humans might prevent SS1P-mediated kidney damage, reduce albumin loss in urine, and alleviate capillary leak syndrome.
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