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Biomedicines 2017, 5(3), 46; doi:10.3390/biomedicines5030046

Comparison of Liver Detargeting Strategies for Systemic Therapy with Oncolytic Adenovirus Serotype 5

1
Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902, USA
2
Virology and Gene Therapy Graduate Program, Mayo Clinic, Rochester, MN 55902, USA
3
Department of Endocrinology, Mayo Clinic, Rochester, MN 55902, USA
4
Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA
5
Department of Immunology, Mayo Clinic, Rochester, MN 55902, USA
*
Author to whom correspondence should be addressed.
Received: 26 July 2017 / Revised: 2 August 2017 / Accepted: 4 August 2017 / Published: 10 August 2017
(This article belongs to the Special Issue Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer)
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Abstract

Oncolytic viruses would ideally be of use for systemic therapy to treat disseminated cancer. To do this safely, this may require multiple layers of cancer specificity. The pharmacology and specificity of oncolytic adenoviruses can be modified by (1) physical retargeting, (2) physical detargeting, (3) chemical shielding, or (4) by modifying the ability of viral early gene products to selectively activate in cancer versus normal cells. We explored the utility of these approaches with oncolytic adenovirus serotype 5 (Ad5) in immunocompetent Syrian hamsters bearing subcutaneous HaK tumors. After a single intravenous injection to reach the distant tumors, the physically hepatocyte-detargeted virus Ad5-hexon-BAP was more effective than conditionally replicating Ad5-dl1101/07 with mutations in its E1A protein. When these control or Ad5 treated animals were treated a second time by intratumoral injection, prior exposure to Ad5 did not affect tumor growth, suggesting that anti-Ad immunity neither prevented treatment nor amplified anti-tumor immune responses. Ad5-dl1101/07 was next chemically shielded with polyethylene glycol (PEG). While 5 kDa of PEG blunted pro-inflammatory IL-6 production induced by Ad5-dl1101/07, this shielding reduced Ad oncolytic activity. View Full-Text
Keywords: adenovirus; conditionally-replicating adenovirus; hexon; PEG adenovirus; conditionally-replicating adenovirus; hexon; PEG
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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

Nguyen, T.V.; Barry, M.E.; Turner, M.A.; Crosby, C.M.; Trujillo, M.A.; Morris, J.C., III; Barry, M.A. Comparison of Liver Detargeting Strategies for Systemic Therapy with Oncolytic Adenovirus Serotype 5. Biomedicines 2017, 5, 46.

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