Loading of oncolytic vesicular stomatitis virus onto antigen-specific T cells enhances the efficacy of adoptive T-cell therapy of tumors

Qiao, J., Wang, H., Kottke, T., Diaz, R., Willmon, C., Hudacek, A., Thompson, J., Parato, K., Bell, J., Naik, J., Chester, John D. ORCID: https://orcid.org/0000-0002-7830-3840, Selby, P., Harrington, K., Melcher, A. and Vile, R. G. 2008. Loading of oncolytic vesicular stomatitis virus onto antigen-specific T cells enhances the efficacy of adoptive T-cell therapy of tumors. Gene Therapy 15 (8) , pp. 604-616. 10.1038/sj.gt.3303098

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Abstract

Although adoptive T-cell therapy has shown clinical success, efficacy is limited by low levels of T-cell trafficking to, and survival in, the immunosuppressive environment of an established tumor. Oncolytic virotherapy has recently emerged as a promising approach to induce both direct tumor cell killing and local proinflammatory environments within tumors. However, inefficient systemic delivery of oncolytic viruses remains a barrier to use of these agents against metastatic disease that is not directly accessible to the end of a needle. Here we show that the ability of antigen-specific T cells to circulate freely, and to localize to tumors, can be exploited to achieve the systemic delivery of replication-competent, oncolytic vesicular stomatitis virus (VSV). Thus, VSV loaded onto OT-I T cells, specific for the SIINFEKL epitope of the ovalbumin antigen, was efficiently delivered to established B16ova tumors in the lungs of fully immune-competent C57Bl/6 mice leading to significant increases in therapy compared to the use of virus, or T cells, alone. Although OT-I T-cell-mediated delivery of VSV led to viral replication within tumors and direct viral oncolysis, therapy was also dependent upon an intact host immune system. Moreover, VSV loading onto the T cells increased both T-cell activation in vitro and T-cell trafficking in vivo. The combination of adoptive T-cell transfer of antigen-specific T cells, along with oncolytic virotherapy, can, therefore, increase the therapeutic utility of both approaches through multiple mechanisms and should be of direct translational value.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	VSV, oncolytic viruses, immunotherapy, adoptive T-cell transfer
Publisher:	Nature Publishing Group
ISSN:	0969-7128
Last Modified:	19 Oct 2022 08:42
URI:	https://orca.cardiff.ac.uk/id/eprint/18796

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