ArticleOncogene2014
Design optimization and characterization of Her2/neu-targeted immunotoxins: comparative in vitro and in vivo efficacy studies.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Molecularly engineered tumor acidity-responsive plant toxin gelonin for safe and efficient cancer therapy.Bioactive materials · 2022Article
- Transient Inhibition of Trastuzumab-Tumor Binding to Overcome the "Binding-Site Barrier" and Improve the Efficacy of a Trastuzumab-Gelonin Immunotoxin.Molecular cancer therapeutics · 2022Article
- The affinity of antigen-binding domain on the antitumor efficacy of CAR T cells: Moderate is better.Frontiers in immunology · 2022Review
- Recombinant immunotoxins development for HER2-based targeted cancer therapies.Cancer cell international · 2021Review
- Targeting Receptors on Cancer Cells with Protein Toxins.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
- Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency.Cancers · 2019Review
- Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe.Scientific reports · 2018Article
- Review
- Structurally Defined αMHC-II Nanobody-Drug Conjugates: A Therapeutic and Imaging System for B-Cell Lymphoma.Angewandte Chemie (International ed. in English) · 2016Article
- Multiformat T-cell-engaging bispecific antibodies targeting human breast cancers.Angewandte Chemie (International ed. in English) · 2015Article
- Photochemical activation of MH3-B1/rGel: a HER2-targeted treatment approach for ovarian cancer.Oncotarget · 2015Article
- Inhibition of cancer cell proliferation and breast tumor targeting of pHLIP-monomethyl auristatin E conjugates.Molecular pharmaceutics · 2015Article
- Recombinant TAT-gelonin fusion toxin: synthesis and characterization of heparin/protamine-regulated cell transduction.Journal of biomedical materials research. Part A · 2015Article
- Combination of antibody targeting and PTD-mediated intracellular toxin delivery for colorectal cancer therapy.Journal of controlled release : official journal of the Controlled Release Society · 2014Article
- Magnetic targeting of novel heparinized iron oxide nanoparticles evaluated in a 9L-glioma mouse model.Pharmaceutical research · 2014Article
- Structural complementation of the catalytic domain of pseudomonas exotoxin A.Journal of molecular biology · 2014Article
- Long-circulating heparin-functionalized magnetic nanoparticles for potential application as a protein drug delivery platform.Molecular pharmaceutics · 2013Article
- Design and Characterization of Ricin Based Immunotoxins Against EPHA2 Receptor for Breast Cancer Therapy: An In-Silico Study.Iranian journal of pharmaceutical research : IJPRArticle
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Targeted therapeutics are potential therapeutic agents because of their selectivity and efficacy against tumors resistant to conventional therapy. The goal of this study was to determine the comparative activity of monovalent, engineered anti-Her2/neu immunotoxins fused to recombinant gelonin (rGel) to the activity of bivalent IgG-containing immunoconjugates. Utilizing Herceptin and its derived humanized single-chain antibody (single-chain fragment variable, designated 4D5), we generated bivalent chemical Herceptin/rGel conjugate, and the corresponding monovalent recombinant immunotoxins in two orientations, 4D5/rGel and rGel/4D5. All the constructs showed similar affinity to Her2/neu-overexpressing cancer cells, but significantly different antitumor activities. The rGel/4D5 orientation construct and Herceptin/rGel conjugate were superior to 4D5/rGel construct in in vitro and in vivo efficacy. The enhanced activity was attributed to improved intracellular toxin uptake into target cells and efficient downregulation of Her2/neu-related signaling pathways. The Her2/neu-targeted immunotoxins effectively targeted cells with Her2/neu expression level >1.5 × 10(5) sites per cell. Cells resistant to Herceptin or chemotherapeutic agents were not cross-resistant to rGel-based immunotoxins. Against SK-OV-3 tumor xenografts, the rGel/4D5 construct with excellent tumor penetration showed impressive tumor inhibition. Although Herceptin/rGel conjugate demonstrated comparatively longer serum half-life, the in vivo efficacy of the conjugate was similar to the rGel/4D5 fusion. These comparative studies demonstrate that the monovalent, engineered rGel/4D5 construct displayed comparable in vitro and in vivo antitumor efficacy as bivalent Herceptin/rGel conjugate. Immunotoxin orientation can significantly impact the overall functionality and performance of these agents. The recombinant rGel/4D5 construct with excellent tumor penetration and rapid blood clearance may reduce the unwanted toxicity when administrating to patients, and warrants consideration for further clinical evaluation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.