ArticleOncotarget2017
HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- A new treatment for canine B-cell lymphoma based on a recombinant single-domain antibody immunotoxin derived fromFrontiers in veterinary science · 2025Article
- Design and construction of scFv-PE35KDEL as a novel immunotoxin against human epidermal growth factor receptor 2 for cancer therapy.Biotechnology letters · 2023Article
- Development and Evaluation of Competitive Inhibitors of Trastuzumab-HER2 Binding to Bypass the Binding-Site Barrier.Frontiers in pharmacology · 2022Article
- Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug.Inorganics · 2021Article
- Recombinant immunotoxins development for HER2-based targeted cancer therapies.Cancer cell international · 2021Review
- Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology.International journal of molecular sciences · 2021Review
- Review
- Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics.Frontiers in oncology · 2020Review
- Multimerization through Pegylation Improves Pharmacokinetic Properties of scFv Fragments of GD2-Specific Antibodies.Molecules (Basel, Switzerland) · 2019Article
- HER2-Specific Targeted Toxin DARPin-LoPE: Immunogenicity and Antitumor Effect on Intraperitoneal Ovarian Cancer Xenograft Model.International journal of molecular sciences · 2019Article
- Penetration Efficiency of Antitumor Agents in Ovarian Cancer Spheroids: The Case of Recombinant Targeted Toxin DARPin-LoPE and the Chemotherapy Drug, Doxorubicin.Pharmaceutics · 2019Article
- Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency.Cancers · 2019Review
- Radioactive (Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Antiviral Immunotoxin AgainstFrontiers in microbiology · 2018Article
- HMonoclonal antibodies in immunodiagnosis and immunotherapy · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody as a targeting module and fragment of Pseudomonas exotoxin A as an effector (toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer cells overexpressing HER2 receptor in vitro and on HER2-positive experimental tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of particular importance in the case of targeted therapeutic agent aimed at personalizing treatment of disease in relation to molecular genetic characteristics of each patient. After specific binding to HER2 on the cell surface and clathrin-mediated endocytosis the immunotoxin passes through retrograde trafficking route. During this route the immunotoxin molecule is supposed to undergo enzymatic processing that ends in separation of C-terminal and N-terminal fragments of the immunotoxin. Finally, C-terminal functionally active fragment of 4D5scFv-PE40 arrests protein synthesis in cytoplasm followed by cell death via apoptosis.
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Registered trials
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.