Oncolytic herpes simplex virus

An anti-invasive therapeutic strategy for paediatric high grade glioma and diffuse intrinsic pontine glioma

Julia V. Cockle, Elizabeth Ilett, Anke Bruning-Richardson, Jill Thompson, Timothy Kottke, Karen Scott, Ewan E. Morrison, Azam Ismail, Ailsa Rose, Susan Picton, Richard Vile, Peter J. Selby, Susan C Short, Alan Melcher

Research output: Contribution to journalMeeting Abstract

Abstract

Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells and/or stimulate an anti-tumour immune response, offers a novel treatment approach. Here, we evaluate the effects of oncolytic herpes simplex virus (HSV) 1716 on migration and invasion in in vitro and in vivo models of pHGG and DIPG. In vitro migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Oncolytic HSV resulted in blockade of both migration and invasion in all pHGG and DIPG cell lines and this did not appear to be a consequence of cytotoxicity or altered proliferation. pHGG cells demonstrated reduced velocity, loss of polarity and changed morphology in the presence of virus. Oncolytic HSV altered pHGG cytoskeletal dynamics, stabilising microtubules through accumulation of post-translational tubulin modifications. Furthermore, oncolytic HSV treatment of pHGG cell lines inhibited glycogen synthase kinase-3 (a key regulator of cell migration and microtubule dynamics) and prevented localised clustering of adenomatous polyposis coli to the leading edge of cells. Importantly, oncolytic HSV treatment reduced tumour infiltration and enhanced therapy in a mouse orthotopic xenograft model of DIPG. In conclusion, this study is the first to demonstrate that it is possible to target migration and invasion of pHGG and DIPG using oncolytic HSV. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG as an anti-invasive agent, improving outcomes for these devastating diseases.
Original languageEnglish
Pages (from-to)49
Number of pages1
JournalNeuro-Oncology
Volume18
Issue numberS3
DOIs
Publication statusPublished - Jun 2016
Externally publishedYes
Event17th International Symposium on Pediatric Neuro-Oncology - Liverpool, United Kingdom
Duration: 12 Jun 201615 Jun 2016
Conference number: 17
http://ispno2016.co.uk/conference-programme/ (Link to Conference Website)

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Oncolytic Viruses
Simplexvirus
Glioma
Pediatrics
Therapeutics
Microtubules
Neoplasms
Oncolytic Virotherapy
Viruses
Glycogen Synthase Kinase 3
Cell Line
Adenomatous Polyposis Coli
Post Translational Protein Processing
Tubulin

Cite this

Cockle, Julia V. ; Ilett, Elizabeth ; Bruning-Richardson, Anke ; Thompson, Jill ; Kottke, Timothy ; Scott, Karen ; Morrison, Ewan E. ; Ismail, Azam ; Rose, Ailsa ; Picton, Susan ; Vile, Richard ; Selby, Peter J. ; Short, Susan C ; Melcher, Alan. / Oncolytic herpes simplex virus : An anti-invasive therapeutic strategy for paediatric high grade glioma and diffuse intrinsic pontine glioma. In: Neuro-Oncology. 2016 ; Vol. 18, No. S3. pp. 49.
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abstract = "Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells and/or stimulate an anti-tumour immune response, offers a novel treatment approach. Here, we evaluate the effects of oncolytic herpes simplex virus (HSV) 1716 on migration and invasion in in vitro and in vivo models of pHGG and DIPG. In vitro migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Oncolytic HSV resulted in blockade of both migration and invasion in all pHGG and DIPG cell lines and this did not appear to be a consequence of cytotoxicity or altered proliferation. pHGG cells demonstrated reduced velocity, loss of polarity and changed morphology in the presence of virus. Oncolytic HSV altered pHGG cytoskeletal dynamics, stabilising microtubules through accumulation of post-translational tubulin modifications. Furthermore, oncolytic HSV treatment of pHGG cell lines inhibited glycogen synthase kinase-3 (a key regulator of cell migration and microtubule dynamics) and prevented localised clustering of adenomatous polyposis coli to the leading edge of cells. Importantly, oncolytic HSV treatment reduced tumour infiltration and enhanced therapy in a mouse orthotopic xenograft model of DIPG. In conclusion, this study is the first to demonstrate that it is possible to target migration and invasion of pHGG and DIPG using oncolytic HSV. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG as an anti-invasive agent, improving outcomes for these devastating diseases.",
author = "Cockle, {Julia V.} and Elizabeth Ilett and Anke Bruning-Richardson and Jill Thompson and Timothy Kottke and Karen Scott and Morrison, {Ewan E.} and Azam Ismail and Ailsa Rose and Susan Picton and Richard Vile and Selby, {Peter J.} and Short, {Susan C} and Alan Melcher",
year = "2016",
month = "6",
doi = "10.1093/neuonc/now073.07",
language = "English",
volume = "18",
pages = "49",
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Cockle, JV, Ilett, E, Bruning-Richardson, A, Thompson, J, Kottke, T, Scott, K, Morrison, EE, Ismail, A, Rose, A, Picton, S, Vile, R, Selby, PJ, Short, SC & Melcher, A 2016, 'Oncolytic herpes simplex virus: An anti-invasive therapeutic strategy for paediatric high grade glioma and diffuse intrinsic pontine glioma', Neuro-Oncology, vol. 18, no. S3, pp. 49. https://doi.org/10.1093/neuonc/now073.07

Oncolytic herpes simplex virus : An anti-invasive therapeutic strategy for paediatric high grade glioma and diffuse intrinsic pontine glioma. / Cockle, Julia V.; Ilett, Elizabeth; Bruning-Richardson, Anke; Thompson, Jill; Kottke, Timothy; Scott, Karen; Morrison, Ewan E.; Ismail, Azam; Rose, Ailsa; Picton, Susan; Vile, Richard; Selby, Peter J.; Short, Susan C; Melcher, Alan.

In: Neuro-Oncology, Vol. 18, No. S3, 06.2016, p. 49.

Research output: Contribution to journalMeeting Abstract

TY - JOUR

T1 - Oncolytic herpes simplex virus

T2 - An anti-invasive therapeutic strategy for paediatric high grade glioma and diffuse intrinsic pontine glioma

AU - Cockle, Julia V.

AU - Ilett, Elizabeth

AU - Bruning-Richardson, Anke

AU - Thompson, Jill

AU - Kottke, Timothy

AU - Scott, Karen

AU - Morrison, Ewan E.

AU - Ismail, Azam

AU - Rose, Ailsa

AU - Picton, Susan

AU - Vile, Richard

AU - Selby, Peter J.

AU - Short, Susan C

AU - Melcher, Alan

PY - 2016/6

Y1 - 2016/6

N2 - Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells and/or stimulate an anti-tumour immune response, offers a novel treatment approach. Here, we evaluate the effects of oncolytic herpes simplex virus (HSV) 1716 on migration and invasion in in vitro and in vivo models of pHGG and DIPG. In vitro migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Oncolytic HSV resulted in blockade of both migration and invasion in all pHGG and DIPG cell lines and this did not appear to be a consequence of cytotoxicity or altered proliferation. pHGG cells demonstrated reduced velocity, loss of polarity and changed morphology in the presence of virus. Oncolytic HSV altered pHGG cytoskeletal dynamics, stabilising microtubules through accumulation of post-translational tubulin modifications. Furthermore, oncolytic HSV treatment of pHGG cell lines inhibited glycogen synthase kinase-3 (a key regulator of cell migration and microtubule dynamics) and prevented localised clustering of adenomatous polyposis coli to the leading edge of cells. Importantly, oncolytic HSV treatment reduced tumour infiltration and enhanced therapy in a mouse orthotopic xenograft model of DIPG. In conclusion, this study is the first to demonstrate that it is possible to target migration and invasion of pHGG and DIPG using oncolytic HSV. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG as an anti-invasive agent, improving outcomes for these devastating diseases.

AB - Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours associated with poor survival. Oncolytic virotherapy, which uses viruses to selectively infect and destroy cancer cells and/or stimulate an anti-tumour immune response, offers a novel treatment approach. Here, we evaluate the effects of oncolytic herpes simplex virus (HSV) 1716 on migration and invasion in in vitro and in vivo models of pHGG and DIPG. In vitro migratory characteristics were examined using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays. Oncolytic HSV resulted in blockade of both migration and invasion in all pHGG and DIPG cell lines and this did not appear to be a consequence of cytotoxicity or altered proliferation. pHGG cells demonstrated reduced velocity, loss of polarity and changed morphology in the presence of virus. Oncolytic HSV altered pHGG cytoskeletal dynamics, stabilising microtubules through accumulation of post-translational tubulin modifications. Furthermore, oncolytic HSV treatment of pHGG cell lines inhibited glycogen synthase kinase-3 (a key regulator of cell migration and microtubule dynamics) and prevented localised clustering of adenomatous polyposis coli to the leading edge of cells. Importantly, oncolytic HSV treatment reduced tumour infiltration and enhanced therapy in a mouse orthotopic xenograft model of DIPG. In conclusion, this study is the first to demonstrate that it is possible to target migration and invasion of pHGG and DIPG using oncolytic HSV. We propose that oncolytic HSV may have therapeutic benefits for pHGG and DIPG as an anti-invasive agent, improving outcomes for these devastating diseases.

U2 - 10.1093/neuonc/now073.07

DO - 10.1093/neuonc/now073.07

M3 - Meeting Abstract

VL - 18

SP - 49

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - S3

ER -