ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 66 citations in OpenAlex.
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- Tumor-infiltrating and circulating B cells mediate local and systemic immunomodulatory mechanisms in Glioblastoma.Journal of neuro-oncology · 2025Review
- Structural insights into the role and targeting of EGFRvIII.Structure (London, England : 1993) · 2024Article
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Cancer Drug Delivery Systems Using Bacterial Toxin Translocation Mechanisms.Bioengineering (Basel, Switzerland) · 2023Review
- Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.Science translational medicine · 2023Article
- Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective.Antibody therapeutics · 2022Review
- Convection-enhanced delivery for high-grade glioma.Neuro-oncology practice · 2022Review
- Engineered antibody fusion proteins for targeted disease therapy.Trends in pharmacological sciences · 2021Review
- New Immunotherapeutic Approaches for Glioblastoma.Journal of immunology research · 2021Review
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- Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience.Pharmaceutics · 2020Review
- Targeting Receptors on Cancer Cells with Protein Toxins.Biomolecules · 2020Review
- Development of Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer: An Update.Biomolecules · 2020Review
- Immunogenicity of Immunotoxins ContainingFrontiers in immunology · 2020Review
- Biological intratumoral therapy for the high-grade glioma part I: intratumoral delivery and immunotoxins.CNS oncology · 2019Review
- Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations.Journal for immunotherapy of cancer · 2019Article
- Hosts for Hostile Protein Production: The Challenge of Recombinant Immunotoxin Expression.Biomedicines · 2019Review
- Synergistic antitumor effects of 9.2.27-PE38KDEL and ABT-737 in primary and metastatic brain tumors.PloS one · 2019Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
purposeThe EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive with a 55-amino acid (AA) region present in the extracellular domain of both EGFRwt (583-637 AAs) and EGFRvIII (292-346 AAs) proteins. EXPERIMENTAL
designThe binding affinity and specificity of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII were measured by surface-plasmon resonance and flow cytometry. In vitro cytotoxicity of D2C7-(scdsFv)-PE38KDEL was measured by inhibition of protein synthesis in human EGFRwt-transfected NR6 (NR6W), human EGFRvIII-transfected NR6 (NR6M), EGFRwt-overexpressing A431-epidermoid-carcinoma, and glioblastoma xenograft cells (43, D08-0493MG, D2159MG, and D270MG). In vivo antitumor efficacy of D2C7-(scdsFv)-PE38KDEL was evaluated using 43, NR6M, and D270MG orthotopic tumor models.
resultsThe KD of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII was 1.6×10(-9) mol/L and 1.3×10(-9) mol/L, respectively. Flow cytometry with NR6W and NR6M cells confirmed the specificity of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII. The D2C7-(scdsFv)-PE38KDEL IC50 was 0.18 to 2.5 ng/mL on cells expressing EGFRwt (NR6W, A431, 43, and D08-0493MG). The D2C7-(scdsFv)-PE38KDEL IC50 was approximately 0.25 ng/mL on EGFRvIII-expressing cells (NR6M) and on EGFRwt- and EGFRvIII-expressing glioblastoma xenograft cells (D2159MG and D270MG). Significantly, in intracranial tumor models of 43, NR6M, and D270MG, treatment with D2C7-(scdsFv)-PE38KDEL by convection-enhanced delivery prolonged survival by 310% (P=0.006), 28% (P=0.002), and 166% (P=0.001), respectively.
conclusionsIn preclinical studies, the D2C7-(scdsFv)-PE38KDEL immunotoxin exhibited significant potential for treating brain tumors expressing EGFRwt, EGFRvIII, or both.
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