Oncotarget

Research Papers:

Genetically coating oncolytic herpes simplex virus with CD47 allows efficient systemic delivery and prolongs virus persistence at tumor site

Xinping Fu, Lihua Tao and Xiaoliu Zhang _

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Oncotarget. 2018; 9:34543-34553. https://doi.org/10.18632/oncotarget.26167

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Abstract

Xinping Fu1, Lihua Tao1 and Xiaoliu Zhang1

1Department of Biology and Biochemistry and Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA

Correspondence to:

Xiaoliu Zhang, email: shaunzhang@uh.edu

Keywords: oncolytic; herpes simplex virus; CD47; systemic delivery; innate antiviral

Received: July 15, 2018     Accepted: September 01, 2018     Published: October 02, 2018

ABSTRACT

Current oncolytic virotherapy is primarily administered by intratumoral injection. However, systemic delivery is desirable for treating patients, particularly for those who have developed metastatic diseases. Several components are impeding the systemic delivery efficiency of oncolytic viruses. Chief among them is the rapid clearance of viral particles by the host’s mononuclear phagocyte system (MPS). We explored the possibility of genetically engrafting CD47, a “don’t eat me” signal molecule, to the membrane envelop of an oncolytic herpes simplex virus (HSV) to enable it to escape from the MPS for systemic delivery. Our results show that this modification indeed allows the virus to be more efficiently delivered to local tumors by the systemic route. Moreover, this modification also prolongs the virus persistence in local tumors after it arrives there. Consequently, systemic delivery of the modified virus produced a measurable antitumor effect against a murine tumor model that is otherwise resistant to the parental virus delivered by the same route. Our data thus suggest that engrafting enveloped oncolytic viruses such as those derived from HSV with CD47 molecule represents a conceivable strategy to enhance the efficiency of systemic delivery.


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