ArticleBritish journal of cancer2009
Design and modification of EGF4KDEL 7Mut, a novel bispecific ligand-directed toxin, with decreased immunogenicity and potent anti-mesothelioma activity.
Article in British journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- AB Toxins as High-Affinity Ligands for Cell Targeting in Cancer Therapy.International journal of molecular sciences · 2023Review
- Impact of repeated cycles of EGF bispecific angiotoxin (eBAT) administered at a reduced interval from doxorubicin chemotherapy in dogs with splenic haemangiosarcoma.Veterinary and comparative oncology · 2020Article
- Blood Outgrowth Endothelial Cells as a Cellular Carrier for Oncolytic Vesicular Stomatitis Virus Expressing Interferon-β in Preclinical Models of Non-Small Cell Lung Cancer.Translational oncology · 2020Article
- 3D Bioprinted In Vitro Metastatic Models via Reconstruction of Tumor Microenvironments.Advanced materials (Deerfield Beach, Fla.) · 2019Article
- Development of a strategy and computational application to select candidate protein analogues with reduced HLA binding and immunogenicity.Immunology · 2018Article
- Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR.Molecular cancer therapeutics · 2017Article
- Recombinant Immunotoxin Therapy of Glioblastoma: Smart Design, Key Findings, and Specific Challenges.BioMed research international · 2017Review
- Article
- A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma.Targeted oncology · 2014Article
- Diphtheria toxin-based targeted toxin therapy for brain tumors.Journal of neuro-oncology · 2013Review
- Immunotoxin targeting CD133(+) breast carcinoma cells.Drug delivery and translational research · 2013Article
- Bispecific targeting of EGFR and uPAR in a mouse model of head and neck squamous cell carcinoma.Oral oncology · 2012Article
- Intracerebral infusion of the bispecific targeted toxin DTATEGF in a mouse xenograft model of a human metastatic non-small cell lung cancer.Journal of neuro-oncology · 2012Article
- Article
- Targeting tumor-initiating cancer cells with dCD133KDEL shows impressive tumor reductions in a xenotransplant model of human head and neck cancer.Molecular cancer therapeutics · 2011Article
- HER2-affitoxin: a potent therapeutic agent for the treatment of HER2-overexpressing tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Article
- A novel bispecific ligand-directed toxin designed to simultaneously target EGFR on human glioblastoma cells and uPAR on tumor neovasculature.Journal of neuro-oncology · 2011Article
- Toxin-based therapeutic approaches.Toxins · 2010Review
- Article
- Bioengineering a unique deimmunized bispecific targeted toxin that simultaneously recognizes human CD22 and CD19 receptors in a mouse model of B-cell metastases.Molecular cancer therapeutics · 2010Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPotency, immunogenicity, and toxicity are three problems that limit the use of targeted toxins in solid tumour therapy.
methodsTo address potency, we used genetic engineering to develop a novel bispecific ligand-directed toxin (BLT) called EGF4KDEL, a novel recombinant anti-mesothelioma agent created by linking human epidermal growth factor (EGF) and interleukin-4 (IL-4) to truncated pseudomonas exotoxin (PE38) on the same single-chain molecule. Immunogenicity was reduced by mutating seven immunodominant B-cell epitopes on the PE38 molecule to create a new agent, EGF4KDEL 7Mut.
resultsIn vitro, bispecific EGF4KDEL showed superior anti-mesothelioma activity compared with its monospecific counterparts. Toxicity in mice was diminished by having both ligands on the same molecule, allowing administration of a 10-fold greater dose of BLT than a mixture of monomeric IL4KDEL and EGFKDEL. EGF4KDEL 7Mut, retained all of its functional activity and induced about 87% fewer anti-toxin antibodies than mice given the parental, non-mutated form. In vivo, intraperitoneal (IP) injection of the BLT showed significant (P<0.01) and impressive effects against two aggressive, malignant IP mesothelioma models when treatment was begun 14-16 days post tumour innoculation.
conclusionThese data show that EGF4KDEL 7Mut is a promising new anti-mesothelioma agent that was developed to specifically address the obstacles facing clinical utility of targeted toxins.
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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.