ArticleNuclear medicine and biology2012
Radioimmunotargeting of malignant glioma by monoclonal antibody D2C7 reactive against both wild-type and variant III mutant epidermal growth factor receptors.
Article in Nuclear medicine and biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- A phase II study of radioimmunotherapy with intraventricularPediatric blood & cancer · 2018Trial
- EGFR-targeted antibody-toxin conjugate in recurrent glioma: a phase 1 trial.Nature medicine · 2026Article
- Structural insights into the role and targeting of EGFRvIII.Structure (London, England : 1993) · 2024Article
- Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective.Antibody therapeutics · 2022Review
- Review
- Targeting Receptors on Cancer Cells with Protein Toxins.Biomolecules · 2020Review
- 'Characterization of monoclonal antibodies generated to the 287-302 amino acid loop of the human epidermal growth factor receptor'.Antibody therapeutics · 2019Article
- Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations.Journal for immunotherapy of cancer · 2019Article
- EGFR heterogeneity and implications for therapeutic intervention in glioblastoma.Neuro-oncology · 2018Review
- Development and validation of a cell-based fluorescent method for measuring antibody affinity.Journal of immunological methods · 2017Article
- Radiolabeled novel mAb 4G1 for immunoSPECT imaging of EGFRvIII expression in preclinical glioblastoma xenografts.Oncotarget · 2017Article
- Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers.Toxins · 2016Review
- EGFR/EGFRvIII-targeted immunotoxin therapy for the treatment of glioblastomas via convection-enhanced delivery.Receptors & clinical investigation · 2016Article
- Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging.Oncotarget · 2015Article
- Synthesis and preliminary evaluation of a new (99m)tc labeled substance p analogue as a potential tumor imaging agent.Iranian journal of pharmaceutical research : IJPR · 2015Article
- Radiolabeling and in vitro evaluation of (67)Ga-NOTA-modular nanotransporter--a potential Auger electron emitting EGFR-targeted radiotherapeutic.Nuclear medicine and biology · 2014Article
- A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma.Oncoimmunology · 2013Article
- Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Passive immunotherapeutic strategies for the treatment of malignant gliomas.Neurosurgery clinics of North America · 2012Review
- Toxin-based targeted therapy for malignant brain tumors.Clinical & developmental immunology · 2012Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
introductionMalignant glioma remains a significant therapeutic challenge, and immunotherapeutics might be a beneficial approach for these patients. A monoclonal antibody (MAb) specific for multiple molecular targets could expand the treatable patient population and the fraction of tumor cells targeted, with potentially increased efficacy. This motivated the generation of MAb D2C7, which recognizes both wild-type epidermal growth factor receptor (EGFRwt) and a tumor-specific mutant, EGFRvIII.
methodsD2C7 binding affinity was determined by surface plasmon resonance and its specificity characterized through comparison to EGFRwt-specific EGFR.1 and EGFRvIII-specific L8A4 MAbs by flow cytometry and immunohistochemical analysis. The three MAbs were labeled with (125)I or (131)I using Iodogen, and paired-label internalization assays and biodistribution experiments in athymic mice with human tumor xenografts were performed.
resultsThe affinity of D2C7 for EGFRwt and EGFRvIII was 5.2×10(9) M(-1) and 3.6×10(9) M(-1), and cell-surface reactivity with both receptors was documented by flow cytometry. Immunohistochemical analyses revealed D2C7 reactivity with malignant glioma tissue from 90 of 101 patients. Internalization assays performed on EGFRwt-expressing WTT cells and EGFRvIII-expressing NR6M cells indicated a threefold lower degradation of (125)I-labeled D2C7 compared with (131)I-labeled EGFR.1. Uptake of (125)I-labeled D2C7 in NR6M xenografts (52.45±13.97 %ID g(-1) on Day 3) was more than twice that of (131)I-labeled L8A4; a threefold to fivefold tumor delivery advantage was seen when compared to (131)I-labeled EGFR.1 in mice with WTT xenografts.
conclusionsThese results suggest that D2C7 warrants further evaluation for the development of MAb-based therapeutics against cancers expressing EGFRwt and EGFRvIII.
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