Evaluating the effects of oncolytic Herpes Simplex Virus (SEPREHVIR) on paediatric high grade glioma viability, migration and invasion: Potential for clinical application

Julia V. Cockle, Elizabeth Ilett, Karen Scott, Anke Bruning-Richardson, Susan Picton, Susan C Short, Alan Melcher

Research output: Contribution to journalMeeting Abstract

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
LanguageEnglish
Number of pages1
JournalHuman Gene Therapy
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 2014
Externally publishedYes
Event8th International Conference on Oncolytic Virus Therapeutics - Lincoln College & Examination Schools , Oxford, United Kingdom
Duration: 10 Apr 201413 Apr 2014
Conference number: 8
https://oncolyticvirusmeeting.weebly.com/ (Link to Conference Website)

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Oncolytic Viruses
Simplexvirus
Glioma
Pediatrics
Cell Line
Neoplasms
Cell Survival
Oncolytic Virotherapy
Therapeutics
Collagen
Viruses
Infection

Cite this

@article{04dd5633319240adb3a1169c723dd7ee,
title = "Evaluating the effects of oncolytic Herpes Simplex Virus (SEPREHVIR) on paediatric high grade glioma viability, migration and invasion: Potential for clinical application",
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",
author = "Cockle, {Julia V.} and Elizabeth Ilett and Karen Scott and Anke Bruning-Richardson and Susan Picton and Short, {Susan C} and Alan Melcher",
year = "2014",
month = "12",
doi = "10.1089/hum.2014.2538.abstracts",
language = "English",
volume = "25",
journal = "Human Gene Therapy",
issn = "1043-0342",
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number = "12",

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Evaluating the effects of oncolytic Herpes Simplex Virus (SEPREHVIR) on paediatric high grade glioma viability, migration and invasion : Potential for clinical application. / Cockle, Julia V.; Ilett, Elizabeth; Scott, Karen; Bruning-Richardson, Anke; Picton, Susan; Short, Susan C; Melcher, Alan.

In: Human Gene Therapy, Vol. 25, No. 12, 12.2014.

Research output: Contribution to journalMeeting Abstract

TY - JOUR

T1 - Evaluating the effects of oncolytic Herpes Simplex Virus (SEPREHVIR) on paediatric high grade glioma viability, migration and invasion

T2 - Human Gene Therapy

AU - Cockle, Julia V.

AU - Ilett, Elizabeth

AU - Scott, Karen

AU - Bruning-Richardson, Anke

AU - Picton, Susan

AU - Short, Susan C

AU - Melcher, Alan

PY - 2014/12

Y1 - 2014/12

N2 - 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

AB - 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

U2 - 10.1089/hum.2014.2538.abstracts

DO - 10.1089/hum.2014.2538.abstracts

M3 - Meeting Abstract

VL - 25

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 12

ER -