ArticleOncolytic virotherapy2018
Oncolytic adenovirus Ad657 for systemic virotherapy against prostate cancer.
Article in Oncolytic virotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
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- Interactomics: Dozens of Viruses, Co-evolving With Humans, Including the Influenza A Virus, may Actively Distort Human Aging.Molecular biology and evolution · 2023Article
- Development of Oncolytic Vectors Based on Human Adenovirus Type 6 for Cancer Treatment.Viruses · 2023Article
- Effects of pre-existing anti-adenovirus antibodies on transgene expression levels and therapeutic efficacies of arming oncolytic adenovirus.Scientific reports · 2022Article
- Binding of adenovirus species C hexon to prothrombin and the influence of hexon on vector properties in vitro and in vivo.PLoS pathogens · 2022Article
- Safe and efficientMolecular therapy. Methods & clinical development · 2022Article
- Modulating Oncolytic Adenovirus Immunotherapy by Driving Two Axes of the Immune System by Expressing 4-1BBL and CD40L.Human gene therapy · 2022Article
- Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy.Pharmaceutics · 2021Review
- Efficient antitumor effects of a novel oncolytic adenovirus fully composed of species B adenovirus serotype 35.Molecular therapy oncolytics · 2021Article
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- Divergent HIV-1-Directed Immune Responses Generated by Systemic and Mucosal Immunization with Replicating Single-Cycle Adenoviruses in Rhesus Macaques.Journal of virology · 2019Article
- Comparison of systemic and mucosal immunization with replicating Single cycle Adenoviruses.Global vaccines and immunology · 2018Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman species C adenovirus serotype 5 (Ad5) is the archetype oncolytic adenovirus and has been used in the vast majority of preclinical and clinical tests. While Ad5 can be robust, species C Ad6 has lower seroprevalence, side effects, and appears to be more potent as a systemic therapy against a number of tumors than Ad5. Historically, there have only been four species C human adenoviruses: serotypes 1, 2, 5, and 6. More recently a new species C adenovirus, Ad57, was identified. Ad57 is most similar to Ad6 with virtually all variation in their capsid proteins occurring in the hypervariable regions (HVRs) of their hexon proteins. Most adenovirus neutralizing antibodies target the HVRs on adenoviruses. This led us to replace the hexon HVRs in Ad6 with those from Ad57 to create a new virus called Ad657 and explore this novel species C platform's utility as an oncolytic virus.
methodsThe HVR region from Ad57 was synthesized and used to replace the Ad6 HVR region by homologous recombination in bacteria generating a new viral platform that we call Ad657. Replication-competent Ad5, Ad6, and Ad657 were compared in vitro and in vivo for liver damage and oncolytic efficacy against prostate cancers after single intravenous treatment in mice.
resultsAd5, Ad6, and Ad657 had similar in vitro oncolytic activity against human prostate cancer cells. Ad5 provoked the highest level of liver toxicity after intravenous injection and Ad657 caused the least damage in mice. Previous data demonstrated that Ad6 was superior to Ad5 at killing distant subcutaneous prostate cancer tumors in mouse models after a intravenous injection. Given this, Ad657 was compared to the Ad6 benchmark virus by single intravenous injection into mice bearing subcutaneous human DU145 prostate cancers. Under these conditions, Ad657 first infected the liver and then reached distant tumors. Both Ad6 and Ad657 mediated significant delays in tumor growth and extension of survival with Ad6 mediating higher efficacy.
conclusionsThese data suggest that Ad657 may have utility as a local or systemic oncolytic virotherapy for prostate cancers. These data also lay the foundation for serotype-switching with oncolytic species C Ads.
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