Oncotarget

Research Papers:

An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites

Xinping Fu, Armando Rivera, Lihua Tao and Xiaoliu Zhang _

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Oncotarget. 2015; 6:902-914. https://doi.org/10.18632/oncotarget.2817

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Abstract

Xinping Fu1,*, Armando Rivera1,*, Lihua Tao1 and Xiaoliu Zhang2

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

2 Department of Biology and Biochemistry, University of Houston, Houston, Texas, USA

* These authors contributed equally to this work

Correspondence:

Xiaoliu Zhang, email:

Keywords: oncolytic virus, adoptive T cell transfer, chemokines, T cell migration, antitumor immunity

Received: October 10, 2014 Accepted: November 24, 2014 Published: November 25, 2014

Abstract

Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor. Moreover, once attracted to the tumor site by the virus, T cells persisted in there significantly longer than in mock-treated tumor. Chemokine profiling identified significant elevation of CXCL9 and CXCL10, as well as several other chemokines belonging to the inflammatory chemokine family in the virus-treated tumors. These chemokines initially guided the T-cell migration to and then maintained their persistence in the tumor site, leading to a significantly enhanced therapeutic effect. Our data suggests that this virotherapy may be combined with adoptive T-cell therapy to potentiate its therapeutic effect against solid tumors that are otherwise difficult to manage with the treatment alone.


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