title: Group B adenovirus enadenotucirev infects polarised colorectal cancer cells efficiently from the basolateral surface expected to be encountered during intravenous delivery to treat disseminated cancer.
abstract: Enadenotucirev (EnAd) is a group B oncolytic adenovirus developed for systemic delivery and currently undergoing clinical evaluation for advanced cancer therapy. For differentiated carcinomas, systemic delivery would likely expose virus particles to the basolateral surface of cancer cells rather than the apical surface encountered during natural infection. Here, we compare the ability of EnAd and adenovirus type-5 (Ad5) to infect polarised colorectal carcinoma cells from the apical or basolateral surfaces. Whereas Ad5 infection was more efficient via the apical than basolateral surface, EnAd readily infected cells from either surface. Progeny particles from EnAd were released preferentially via the apical surface for all cell lines and routes of infection. These data further support the utility of group B adenoviruses for systemic delivery and suggest that progeny virus are more likely to be released into the tumour rather than back through the basolateral surface into the blood stream.
authors.affiliation: Department of Oncology, University of Oxford, Oxford, United Kingdom; Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Suet-Lin
authors.initials: SL
authors.lastname: Chia
authors.affiliation: Department of Oncology, University of Oxford, Oxford, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Lei
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: David J P
authors.initials: DJP
authors.lastname: Ferguson
authors.affiliation: Department of Oncology, University of Oxford, Oxford, United Kingdom.
authors.forename: Arthur
authors.initials: A
authors.lastname: Dyer
authors.affiliation: Department of Oncology, University of Oxford, Oxford, United Kingdom; PsiOxus Therapeutics, Abingdon, United Kingdom.
authors.forename: Kerry D
authors.initials: KD
authors.lastname: Fisher
authors.affiliation: Department of Oncology, University of Oxford, Oxford, United Kingdom. Electronic address: len.seymour@oncology.ox.ac.uk.
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Seymour
mesh_terms: D000260:Adenoviruses, Human / Q000145:classification / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D016764:Cell Polarity; D015179:Colorectal Neoplasms / Q000628:therapy*; D004847:Epithelial Cells / Q000821:virology; D019073:HT29 Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000145:classification / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D000970:Antineoplastic Agents; D011991:Receptors, Virus
keywords: Adenovirus; Cell polarisation; Colorectal cancer; Oncolytic virus; Tight junctions; Tumour infiltration