Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles

Abstract

Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. In 2006, the world witnessed the first government-approved oncolytic virus for the treatment of head and neck cancer. It has been known for many years that viruses have the ability to replicate in and lyse cancer cells. Although encouraging results have been demonstrated in vitro and in animal models, most oncolytic viruses have failed to impress in the clinical setting. The explanation is multifactorial, determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immune response. This review focuses on discussion of the obstacles that oncolytic virotherapy faces and recent advances made to overcome them, with particular reference to adenoviruses.

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

“…39 HSV 1 can reduce apoptosis via the ICP 34.5 gene product, which modifies the protein kinase R pathway, blocking the apoptotic mechanism in normal cells. [39][40][41][42] The effects of oncolytic herpes viruses on apoptosis are controversial: apoptosis is elevated upon viral treatment in some studies, 43,44 but reduced in others. 45,46 Some have argued that induction of premature apoptosis is not a desirable feature of oncolytic viral treatment; 47 instead, reducing or delaying apoptosis may enhance viral penetration of the tumor, another determinant of the potency of an oncolytic virus.…”

Anticancer Gene Transfer for Cancer Gene Therapy

“…Moreover, fusion of two different enzymes has been employed for increased killing efficacy, in difficult to target cancers. The majority of the viruses that have been used to deliver these genes were nonreplicative but recently replication-able oncolytics have been employed for pro-drug suicidal strategy (Wong et al, 2010).…”

Evaluating optimal therapy robustness by virtual expansion of a sample population, with a case study in cancer immunotherapy

“…This process requires the identification of the optimal protocol (possibly among a list of clinically viable options) for each of the virtual populations, followed by an analysis of responses to the optimal protocol(s) across the virtual populations. (32). Lysis results in the release of more OVs that can infect additional tumor cells, spreading an infection throughout the tumor that, in theory, results in tumor regression while sparing normal cells.…”

“…Lysis results in the release of more OVs that can infect additional tumor cells, spreading an infection throughout the tumor that, in theory, results in tumor regression while sparing normal cells. These OVs can be further genetically enhanced to act as a vector for delivering therapeutic genes to the tumor site (32). In ref.…”