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Oncolytic Vaccinia virus and radiotherapy in head and neck cancer

Authors :
Richard G. Vile
Joan N. Kyula
Aadil A. Khan
R. Seth
Victoria Roulstone
David Mansfield
T. Pencavel
Kevin J. Harrington
Shane Zaidi
Yann Touchefeu
L. Karapanagiotou
Martin McLaughlin
Alan Melcher
Khin Thway
Hardev Pandha
Source :
Oral Oncology. 49:108-118
Publication Year :
2013
Publisher :
Elsevier BV, 2013.

Abstract

Summary Objective Oncolytic forms of attenuated Vaccinia virus are now in clinical development, assessing the compatibility of this novel treatment with radiotherapy may reveal exploitable synergistic relationships. Materials and methods In vitro analyses of cell killing, cell cycle effects and caspase activation were carried out on HN3, HN5, CAL27, Detroit, SIHN5B, and PJ41 cells. In vivo studies of the virus and X-radiation were performed on H&N xenografts in CD1 nude mice. Results Cell killing in vitro was demonstrated to be dose- and time-dependent. Infection causes an increase in S-phase and sub-G1 cells. A dose dependent increase in active caspase-3 indicated induction of apoptosis. Xenografts injected with Vaccinia stabilised and frequently completely regressed. Combination with radiation generated additional cell death, induction of caspase activity and in vivo further improved long term regression rates. Conclusions These data support continued exploration of this therapy combination and indicates potential for clinical trials in head and neck cancer.

Details

ISSN :
13688375
Volume :
49
Database :
OpenAIRE
Journal :
Oral Oncology
Accession number :
edsair.doi.dedup.....b4273e1671490ab56f5f00941334e1e8
Full Text :
https://doi.org/10.1016/j.oraloncology.2012.07.019