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Arming viruses in multi-mechanistic oncolytic viral therapy: current research and future developments, with emphasis on poxviruses

Authors Sampath P, Thorne S

Received 4 September 2013

Accepted for publication 7 November 2013

Published 6 December 2013 Volume 2014:3 Pages 1—9

DOI https://doi.org/10.2147/OV.S36703

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 7


Padma Sampath, Steve H Thorne

Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA

Abstract: The field of oncolytic virology has made great strides in recent years. However, one key finding has been that the use of viral agents that replicate selectively in tumors is usually insufficient to achieve anything beyond small and transient responses. Instead, like most cancer therapies, oncolytic viruses are most effective in combination with other therapies, which is where they have proven therapeutic effects in clinical and preclinical studies. In cases of some of the smaller RNA viruses, effects can only be achieved through combination regimens with chemotherapy, radiotherapy, or targeted conventional therapies. However, larger DNA viruses are able to express one or more transgenes; thus, therapeutic mechanisms can be built into the viral vector itself. The incorporated approaches into arming oncolytic viruses through transgene expression will be the main focus of this review, including use of immune activators, prodrug converting enzymes, anti-angiogenic factors, and targeting of the stroma. This will focus on poxviruses as model systems with large cloning capacities, which have routinely been used as transgene expression vectors in different settings, including vaccine and oncolytic viral therapy.

Keywords: vaccinia, poxvirus, immunotherapy, angiogenesis, prodrug

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