ArticleInternational journal of molecular sciences2020
Generation of an Oncolytic Herpes Simplex Viral Vector Completely Retargeted to the GDNF Receptor GFRα1 for Specific Infection of Breast Cancer Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Engineering HSV-1 for oncolytic therapy: From molecular entry mechanisms to retargeting strategies.Genes & diseases · 2026Review
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Next-generation replication-defective HSV vectors for delivery of large DNA payloads.Molecular therapy : the journal of the American Society of Gene Therapy · 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
- Smart Nanobiomaterials for Gene Delivery in Localized Cancer Therapy: An Overview from Emerging Materials and Devices to Clinical Applications.Current cancer drug targets · 2025Review
- 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
- Viruses as tools in gene therapy, vaccine development, and cancer treatment.Archives of virology · 2022Review
- Immunotherapeutic Efficacy of Retargeted oHSVs Designed for Propagation in an Ad Hoc Cell Line.Cancers · 2021Review
- Generation of a Novel Mesothelin-Targeted OncolyticInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Oncolytic herpes simplex viruses (oHSV) are under development for the treatment of a variety of human cancers, including breast cancer, a leading cause of cancer mortality among women worldwide. Here we report the design of a fully retargeted oHSV for preferential infection of breast cancer cells through virus recognition of GFRα1, the cellular receptor for glial cell-derived neurotrophic factor (GDNF). GFRα1 displays a limited expression profile in normal adult tissue, but is upregulated in a subset of breast cancers. We generated a recombinant HSV expressing a completely retargeted glycoprotein D (gD), the viral attachment/entry protein, that incorporates pre-pro-GDNF in place of the signal peptide and HVEM binding domain of gD and contains a deletion of amino acid 38 to eliminate nectin-1 binding. We show that GFRα1 is necessary and sufficient for infection by the purified recombinant virus. Moreover, this virus enters and spreads in GFRα1-positive breast cancer cells in vitro and caused tumor regression upon intratumoral injection in vivo. Given the heterogeneity observed between and within individual breast cancers at the molecular level, these results expand our ability to deliver oHSV to specific tumors and suggest opportunities to enhance drug or viral treatments aimed at other receptors.
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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.