ArticleMolecular therapy. Methods & clinical development2020
Point Mutations in Retargeted gD Eliminate the Sensitivity of EGFR/EGFRvIII-Targeted HSV to Key Neutralizing Antibodies.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Virus Against Cancer: Paradigm-Shifting Biological Concepts.Current neurology and neuroscience reports · 2025Review
- Viral and cellular insulators promote sustained HSV vector-mediated transgene expression in brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Oncolytic herpes simplex viruses designed for targeted treatment of EGFR-bearing tumors.Molecular therapy. Oncology · 2024Article
- Novel mutations in UMolecular therapy. Methods & clinical development · 2023Article
- Modelling the spatial dynamics of oncolytic virotherapy in the presence of virus-resistant tumour cells.PLoS computational biology · 2022Article
- Review
- Treatment of glioblastoma with current oHSV variants reveals differences in efficacy and immune cell recruitment.Molecular therapy oncolytics · 2021Article
- Oncolytic virotherapy reverses the immunosuppressive tumor microenvironment and its potential in combination with immunotherapy.Cancer cell international · 2021Review
- Current strategies to circumvent the antiviral immunity to optimize cancer virotherapy.Journal for immunotherapy of cancer · 2021Review
- Immunotherapeutic Efficacy of Retargeted oHSVs Designed for Propagation in an Ad Hoc Cell Line.Cancers · 2021Review
- Entry of Alphaherpesviruses.Current issues in molecular biology · 2021Review
- Generation of an Oncolytic Herpes Simplex Viral Vector Completely Retargeted to the GDNF Receptor GFRα1 for Specific Infection of Breast Cancer Cells.International journal of molecular sciences · 2020Article
- Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy.International journal of molecular sciences · 2020Review
- A New Era in Oncology: Clinical Insights Into the Application of Oncolytic Viruses.Cancer control : journal of the Moffitt Cancer CenterReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Effective oncolytic virotherapy may require systemic delivery, tumor targeting, and resistance to virus-neutralizing (VN) antibodies. Since herpes simplex virus (HSV) glycoprotein D (gD) is the viral attachment/entry protein and predominant VN target, we examined the impact of gD retargeting alone and in combination with alterations in dominant VN epitopes on virus susceptibility to VN antibodies. We compared the binding of a panel of anti-gD monoclonal antibodies (mAbs) that mimic antibody specificities in human HSV-immune sera to the purified ectodomains of wild-type and retargeted gD, revealing the retention of two prominent epitopes. Substitution of a key residue in each epitope, separately and together, revealed that both substitutions (1) blocked retargeted gD recognition by mAbs to the respective epitopes, and, in combination, caused a global reduction in mAb binding; (2) protected against fusion inhibition by VN mAbs reactive with each epitope in virus-free cell-cell fusion assays; and (3) increased the resistance of retargeted HSV-1 to these VN mAbs. Although the combined modifications of retargeted gD allowed bona fide retargeting, incorporation into virions was partially compromised. Our results indicate that stacking of epitope mutations can additively block retargeted gD recognition by VN antibodies but also that improvements in gD incorporation into virus particles may be required.
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