Under Pressure: Elevated Blood Pressure Enhances Targeting of Tumors by Oncolytic Viruses

Seymour, Leonard W.; Fisher, Kerry D.

doi:10.1038/mt.2016.19

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…Crucially, the survival in the 5% isoflurane group was not statistically significant compared to the saline control group [133]. It has also been noted that the findings in this study, showing the impact of anesthesia on IT pressure and hence perfusion in murine models, provides strong evidence for the need for standardized animal handling and anesthesia protocols [134]. It has been suggested that difference in these practices could be a reason why there has been variability in delivery and efficacy of similar therapeutics used in different facilities.…”

Section: Altering the Internal Pressure Gradient Studiesmentioning

confidence: 53%

Achieving systemic delivery of oncolytic viruses

Hill

Carlisle

2019

Expert Opinion on Drug Delivery

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Introduction: Oncolytic virotherapy is a selective and powerful tool for cancer treatment. Studies proving the ability of oncolytic viruses (OVs) to target and rapidly kill cancer cells have led to approval of H101 and Imlygic®. Both these OVs are restricted to intratumoral administration into cancer lesions. Despite promising preclinical results, systemic delivery of OV has shown limited success in patients due to a knockdown in infectivity, as a result of rapid immune-mediated neutralization, and poor penetration into tumors. Areas covered: This review catalogs the techniques used to enhance OV delivery. Firstly, insights from clinical trials of OV provide evidence of the need for enhanced delivery strategies. Secondly, the techniques applied to overcome the challenges highlighted by clinical trial data (i.e. suboptimal pharmacokinetics, antiviral immune responses, and poor penetration into solid tumors) are reviewed. Expert opinion: For OV to gain traction and convert potential into value, researchers focussed on showing clinical and commercial viability following intratumoral injection. For the technology to mature and become applicable across a wider range of patients/cancer indications, amenability to systemic delivery is required. This may be achieved using strategies that modulate the OV by genetic or chemical means and/or that alter the physiology of target tumors. ARTICLE HISTORY

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Section: Altering the Internal Pressure Gradient Studiesmentioning

confidence: 53%

Achieving systemic delivery of oncolytic viruses

Hill

Carlisle

2019

Expert Opinion on Drug Delivery

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“…Consistent with this blocking treatment, induced edema with HMGB1-blocking antibodies or cilengitide has been shown to increase the therapeutic efficacy of this approach [102,128,129]. It must be noted that the reverse effect has been noted in situations where virus is delivered systemically [130][131][132]. Aside from interstitial pressure, extracellular tumor ECM has also been shown to limit the spread of oncolytic viruses.…”

Section: Increasing Ohsv Spread Into the Tumor Cellsmentioning

confidence: 84%

Replication and Spread of Oncolytic Herpes Simplex Virus in Solid Tumors

Hong

Sahu

Mullarkey

et al. 2022

Viruses

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Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells.

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