NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer

Leung, E. Y.L. et al. (2020) NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer. Molecular Therapy - Oncolytics, 16, pp. 289-301. (doi: 10.1016/j.omto.2020.02.001) (PMID:32195317) (PMCID:PMC7068056)

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Abstract

Oncolytic viruses (OVs) can trigger profound innate and adaptive immune responses, which have the potential both to potentiate and reduce the activity of OVs. Natural killer (NK) cells can mediate potent anti-viral and anti-tumoral responses, but there are no data on the role of NK cells in oncolytic adenovirus activity. Here, we have used two different oncolytic adenoviruses-the Ad5 E1A CR2-deletion mutant 922-947 (group C) and the chimeric Ad3/Ad11p mutant enadenotucirev (group B)-to investigate the effect of NK cells on overall anti-cancer efficacy in ovarian cancer. Because human adenoviruses do not replicate in murine cells, we utilized primary human NK cells from peripheral blood and ovarian cancer ascites. Our results show that 922-947 and enadenotucirev do not infect NK cells, but induce contact-dependent activation and anti-cancer cytotoxicity against adenovirus-infected ovarian cancer cells. Moreover, manipulation of NK receptors DNAM-1 (DNAX accessory molecule-1) and TIGIT (T cell immunoreceptor with Ig and ITIM domains) significantly influences NK cytotoxicity against adenovirus-infected cells. Together, these results indicate that NK cells act to increase the activity of oncolytic adenovirus in ovarian cancer and suggest that strategies to augment NK activity further via the blockade of inhibitory NK receptor TIGIT could enhance therapeutic potential of OVs.

Item Type:Articles
Keywords:Adenovirus, DNAM-1, NK cell, oncolytic virus, ovarian cancer, TIGIT.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hansell, Dr Chris and Mcneish, Professor Iain and Spiliopoulou, Dr Pavlina and Leung, Dr Elaine and Ennis, Dr Darren and Dowson, Miss Suzanne and Farquharson, Dr Malcolm and Carlin, Dr Leo and Graham, Professor Gerard
Authors: Leung, E. Y.L., Ennis, D. P., Kennedy, P. R., Hansell, C., Dowson, S., Farquharson, M., Spiliopoulou, P., Nautiyal, J., McNamara, S., Carlin, L. M., Fisher, K., Davis, D. M., Graham, G., and McNeish, I. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Molecular Therapy - Oncolytics
Publisher:Elsevier (Cell Press)
ISSN:2372-7705
ISSN (Online):2372-7705
Published Online:15 February 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Molecular Therapy - Oncolytics 16: 289-301
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
169374NK cells and oncolytic virus therapy in ovarian cancerIain McNeishWellcome Trust (WELLCOTR)102746/Z/13/ZCS - Clinical Research Garscube
169615Personalised biomarkers of response in high-grade serious ovarian cancerIain McNeishCancer Research UK (CRUK)C608/A15973CS - Clinical Research Garscube
172604Developing personalised therapy for women with ovarian cancerPatricia RoxburghBeatson Cancer Charity (BEATCANC)15-16-051CS - Clinical Research Garscube