Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Efficient Intravenous Tumor Targeting Using the αVβ6 Integrin Selective Precision Virotherapy Ad5NULL-A20

Version 1 : Received: 29 March 2021 / Approved: 31 March 2021 / Online: 31 March 2021 (15:30:59 CEST)

A peer-reviewed article of this Preprint also exists.

Davies, J.A.; Marlow, G.; Uusi-Kerttula, H.K.; Seaton, G.; Piggott, L.; Badder, L.M.; Clarkson, R.W.E.; Chester, J.D.; Parker, A.L. Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5NULL-A20. Viruses 2021, 13, 864. Davies, J.A.; Marlow, G.; Uusi-Kerttula, H.K.; Seaton, G.; Piggott, L.; Badder, L.M.; Clarkson, R.W.E.; Chester, J.D.; Parker, A.L. Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5NULL-A20. Viruses 2021, 13, 864.

Journal reference: Viruses 2021, 13, 864
DOI: 10.3390/v13050864

Abstract

Background: We previously developed a refined, tumor selective adenovirus, Ad5NULL-A20, har-boring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6 positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 hours post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6 selective manner, whilst cell killing me-diated by oncolytic Ad5NULL-A20 was αvβ6 selective. Biodistribution analysis following intrave-nous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor: liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20 based virotherapies efficiently target αvβ6 integrin positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic ap-plications, enabling tumor selective overexpression of virally encoded therapeutic transgenes.

Keywords

Adenovirus; Oncolytic; Virotherapy; Targeting; αvβ6 integrin; Systemic delivery

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.