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Review
. 2016 Feb 16;114(4):357-61.
doi: 10.1038/bjc.2015.481. Epub 2016 Jan 14.

Oncolytic viruses: finally delivering

Leonard W Seymour  1 , Kerry D Fisher  1
Affiliations
Review

Oncolytic viruses: finally delivering

Leonard W Seymour et al. Br J Cancer. .

Abstract

Oncolytic viruses can be found at the confluence of virology, genetic engineering and pharmacology where versatile platforms for molecularly targeted anticancer agents can be designed and optimised. Oncolytic viruses offer several important advantages over traditional approaches, including the following. (1) Amplification of the active agent (infectious virus particles) within the tumour. This avoids unnecessary exposure to normal tissues experienced during delivery of traditional stoichiometric chemotherapy and maximises the therapeutic index. (2) The active cell-killing mechanisms, often independent of programmed death mechanisms, should decrease the emergence of acquired drug resistance. (3) Lytic death of cancer cells provides a pro-inflammatory microenvironment and the potential for induction of an anticancer vaccine response. (4) Tumour-selective expression and secretion of encoded anticancer biologics, providing a new realm of potent and cost-effective-targeted therapeutics.

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Conflict of interest statement

LS and KF both hold equity in PsiOxus Therapeutics Ltd. LS is Chair of Psioxus' Scientific Advisory Committee and KF serves as its Chief Scientific Officer.

Figures

Figure 1
Figure 1
The hallmarks of adenovirus infection. Cellular phenotypic adaptations associated with cancer, known as the ‘Hallmarks of cancer' (Hanahan and Weinberg, 2011) bear many similarities to the ‘Hallmarks of virus infection' of normal cells. This may contribute to the cancer selectivity often associated with lytic viruses, and underlies the concept of design of oncolytic viruses for cancer selectivity through phenotypic complementation.
Figure 2
Figure 2
Armed oncolytic viruses. Oncolytic viruses can be ‘armed' to express therapeutic proteins within infected tumour cells, and secrete them into the tumour microenvironment. This can provide high-level tumour-selective expression of biologics, maximising local activity and minimising systemic toxicities. If the virus is suitable for systemic delivery, this provides the intriguing concept of localised therapy in disseminated tumours following intravenous delivery. AntiCTLA4=checkpoint inhibitor antibody; BiTE=Bi-specific T-cell engager, for modulating activity and tropism of T cells; NIS=sodium iodide symporter (for SPECT imaging of virus activity); NTR=nitroreductase TNF=tumour necrosis factor.
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