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Article

Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5NULL-A20

1
Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
2
School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UK
3
Velindre Cancer Centre, Cardiff CF14 2TL, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Elizabeth Ilett and Fiona Errington-Mais
Viruses 2021, 13(5), 864; https://doi.org/10.3390/v13050864
Received: 29 March 2021 / Revised: 29 April 2021 / Accepted: 4 May 2021 / Published: 8 May 2021
(This article belongs to the Special Issue Oncolytic Viruses Therapy)
We previously developed a refined, tumor-selective adenovirus, Ad5NULL-A20, harboring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20-mer 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 h post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6-selective manner, whilst cell killing mediated by oncolytic Ad5NULL-A20 was αvβ6-selective. Biodistribution analysis following intravenous 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-to-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 applications, enabling tumor-selective overexpression of virally encoded therapeutic transgenes. View Full-Text
Keywords: adenovirus; oncolytic; virotherapy; targeting; αvβ6 integrin; systemic delivery adenovirus; oncolytic; virotherapy; targeting; αvβ6 integrin; systemic delivery
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MDPI and ACS Style

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. https://doi.org/10.3390/v13050864

AMA Style

Davies JA, Marlow G, Uusi-Kerttula HK, Seaton G, Piggott L, Badder LM, Clarkson RWE, Chester JD, Parker AL. Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5NULL-A20. Viruses. 2021; 13(5):864. https://doi.org/10.3390/v13050864

Chicago/Turabian Style

Davies, James A., Gareth Marlow, Hanni K. Uusi-Kerttula, Gillian Seaton, Luke Piggott, Luned M. Badder, Richard W.E. Clarkson, John D. Chester, and Alan L. Parker 2021. "Efficient Intravenous Tumor Targeting Using the αvβ6 Integrin-Selective Precision Virotherapy Ad5NULL-A20" Viruses 13, no. 5: 864. https://doi.org/10.3390/v13050864

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