Abstract
Paediatric high grade gliomas (pHGGs) are devastating tumours with five year survival outcomes between 15–35%. Despite aggressive management, tumours inevitably recur due to their diffuse and invasive nature and novel therapeutics are needed. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells as well as to stimulate an anti-tumour immune response, offers a novel treatment approach. Here we evaluate the in vitro cytotoxic effects of the oncolytic virus herpes simplex virus (HSV) 1716 (SEPREHVIR), on a panel of paediatric glioma cell lines. We also describe for the first time, the effect of HSV1716 on the migratory behavior of pHGG cells.
Cell viability was examined over 96 hours by MTT and FACS-based assays. Migratory behavior was examined using both 2D scratch assays and 3D spheroid invasion assays in collagen. The sensitivity of pHGG lines to HSV1716 was demonstrated by a loss of cell viability over 96 hours (20–40% viability on MTT assay and up to 30% death with live/dead assay by 96 hours of treatment). Analysis of migratory and invasion assays indicated that HSV1716 at multiplicity of infection 10, resulted in a near total blockade of both migration at 24 hours and invasion at 72 hours, in all cell lines tested.
Our results demonstrate that pHGG cell lines are sensitive to the cytolytic effects of HSV1716. Moreover, for the first time, we have shown that HSV can block the migration and invasion of paediatric glioma cells in vitro. We propose that oncolytic viruses may have therapeutic benefits for pHGG, not only as a cytotoxic and immunogenic therapy, but also as anti-invasive agents, potentially improving outcome for this devastating disease
Cell viability was examined over 96 hours by MTT and FACS-based assays. Migratory behavior was examined using both 2D scratch assays and 3D spheroid invasion assays in collagen. The sensitivity of pHGG lines to HSV1716 was demonstrated by a loss of cell viability over 96 hours (20–40% viability on MTT assay and up to 30% death with live/dead assay by 96 hours of treatment). Analysis of migratory and invasion assays indicated that HSV1716 at multiplicity of infection 10, resulted in a near total blockade of both migration at 24 hours and invasion at 72 hours, in all cell lines tested.
Our results demonstrate that pHGG cell lines are sensitive to the cytolytic effects of HSV1716. Moreover, for the first time, we have shown that HSV can block the migration and invasion of paediatric glioma cells in vitro. We propose that oncolytic viruses may have therapeutic benefits for pHGG, not only as a cytotoxic and immunogenic therapy, but also as anti-invasive agents, potentially improving outcome for this devastating disease
| Original language | English |
|---|---|
| Number of pages | 1 |
| Journal | Human Gene Therapy |
| Volume | 25 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2014 |
| Externally published | Yes |
| Event | 8th International Conference on Oncolytic Virus Therapeutics - Lincoln College & Examination Schools , Oxford, United Kingdom Duration: 10 Apr 2014 → 13 Apr 2014 Conference number: 8 https://oncolyticvirusmeeting.weebly.com/ (Link to Conference Website) |
