ArticleOncotarget2016
Pseudotyped αvβ6 integrin-targeted adenovirus vectors for ovarian cancer therapies.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Identification of a novel fiber shaft structural motif and overexpression of key transcripts elucidated in human adenovirus D 10.PLoS pathogens · 2026Article
- Article
- A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications.Molecular therapy. Methods & clinical development · 2024Article
- Review
- Capture and inactivation of viral particles from bioaerosols by electrostatic precipitation.iScience · 2023Article
- Article
- Broad sialic acid usage amongst species D human adenovirus.Npj viruses · 2023Article
- Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?Human gene therapy · 2022Review
- Development of a low-seroprevalence, αvβ6 integrin-selective virotherapy based on human adenovirus type 10.Molecular therapy oncolytics · 2022Article
- The Feasibility of Pressurised Intraperitoneal Aerosolised Virotherapy (PIPAV) to Administer Oncolytic Adenoviruses.Pharmaceutics · 2021Article
- Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5Viruses · 2021Article
- Understanding and addressing barriers to successful adenovirus-based virotherapy for ovarian cancer.Cancer gene therapy · 2021Review
- Species D Adenoviruses as Oncolytic Viral Vectors.Viruses · 2020Article
- Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies.Cancers · 2020Review
- Review
- Expression of Integrin β6 and HAX-1 Correlates with Aggressive Features and Poor Prognosis in Esophageal Squamous Cell Carcinoma.Cancer management and research · 2020Article
- Human adenovirus type 26 uses sialic acid-bearing glycans as a primary cell entry receptor.Science advances · 2019Article
- Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions.Nature communications · 2019Article
- Human adenovirus type 17 from species D transduces endothelial cells and human CD46 is involved in cell entry.Scientific reports · 2018Article
- Oncolytic virus immunotherapies in ovarian cancer: moving beyond adenoviruses.Porto biomedical journal · 2018Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Encouraging results from recent clinical trials are revitalizing the field of oncolytic virotherapies. Human adenovirus type 5 (HAdV-C5/Ad5) is a common vector for its ease of manipulation, high production titers and capacity to transduce multiple cell types. However, effective clinical applications are hindered by poor tumor-selectivity and vector neutralization. We generated Ad5/kn48 by pseudotyping Ad5 with the fiber knob domain from the less seroprevalent HAdV-D48 (Ad48). The vector was shown to utilize coxsackie and adenovirus receptor (CAR) but not CD46 for cell entry. A 20-amino acid peptide NAVPNLRGDLQVLAQKVART (A20) was inserted into the Ad5. Luc HI loop (Ad5.HI.A20) and Ad5/kn48 DG loop (Ad5/kn48.DG.A20) to target a prognostic cancer cell marker, αvβ6 integrin. Relative to the Ad5.Luc parent vector, Ad5.HI.A20, Ad5.KO1.HI.A20 (KO1, ablated CAR-binding) and Ad5/kn48.DG.A20 showed ~ 160-, 270- and 180-fold increased transduction in BT-20 breast carcinoma cells (αvβ6high). Primary human epithelial ovarian cancer (EOC) cultures derived from clinical ascites provided a useful ex vivo model for intraperitoneal virotherapy. Ad5.HI.A20, Ad5.KO1.HI.A20 and Ad5/kn48.DG.A20 transduction was ~ 70-, 60- and 16-fold increased relative to Ad5.Luc in EOC cells (αvβ6high), respectively. A20 vectors transduced EOC cells at up to ~ 950-fold higher efficiency in the presence of neutralizing ovarian ascites, as compared to Ad5.Luc. Efficient transduction and enhanced cancer-selectivity via a non-native αvβ6-mediated route was demonstrated, even in the presence of pre-existing anti-Ad5 immunity. Consequently, αvβ6-targeted Ad vectors may represent a promising platform for local intraperitoneal treatment of ovarian cancer metastases.
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