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Viruses 2015, 7(11), 6009-6042; doi:10.3390/v7112923

Oncolytic Adenovirus: Strategies and Insights for Vector Design and Immuno-Oncolytic Applications

Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
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Author to whom correspondence should be addressed.
Academic Editors: Martine L.M. Lamfers and E. Antonio Chiocca
Received: 30 September 2015 / Revised: 13 November 2015 / Accepted: 17 November 2015 / Published: 24 November 2015
(This article belongs to the Special Issue Oncolytic Viruses)
View Full-Text   |   Download PDF [2195 KB, uploaded 25 November 2015]   |  

Abstract

Adenoviruses (Ad) are commonly used both experimentally and clinically, including oncolytic virotherapy applications. In the clinical area, efficacy is frequently hampered by the high rates of neutralizing immunity, estimated as high as 90% in some populations that promote vector clearance and limit bioavailability for tumor targeting following systemic delivery. Active tumor targeting is also hampered by the ubiquitous nature of the Ad5 receptor, hCAR, as well as the lack of highly tumor-selective targeting ligands and suitable targeting strategies. Furthermore, significant off-target interactions between the viral vector and cellular and proteinaceous components of the bloodstream have been documented that promote uptake into non-target cells and determine dose-limiting toxicities. Novel strategies are therefore needed to overcome the obstacles that prevent efficacious Ad deployment for wider clinical applications. The use of less seroprevalent Ad serotypes, non-human serotypes, capsid pseudotyping, chemical shielding and genetic masking by heterologous peptide incorporation are all potential strategies to achieve efficient vector escape from humoral immune recognition. Conversely, selective vector arming with immunostimulatory agents can be utilized to enhance their oncolytic potential by activation of cancer-specific immune responses against the malignant tissues. This review presents recent advantages and pitfalls occurring in the field of adenoviral oncolytic therapies. View Full-Text
Keywords: adenovirus; oncolytic; virotherapy; immune epitope; neutralization; genetic masking; chimeric vector; pseudotyping; cancer immunotherapy adenovirus; oncolytic; virotherapy; immune epitope; neutralization; genetic masking; chimeric vector; pseudotyping; cancer immunotherapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Uusi-Kerttula, H.; Hulin-Curtis, S.; Davies, J.; Parker, A.L. Oncolytic Adenovirus: Strategies and Insights for Vector Design and Immuno-Oncolytic Applications. Viruses 2015, 7, 6009-6042.

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