NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer

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NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer. / Leung, Elaine Y.l.; Ennis, Darren P.; Kennedy, Philippa R.; Hansell, Christopher; Dowson, Suzanne; Farquharson, Malcolm; Spiliopoulou, Pavlina; Nautiyal, Jaya; Mcnamara, Sophie; Carlin, Leo M.; Fisher, Kerry; Davis, Daniel M.; Graham, Gerard; Mcneish, Iain A.

In: Molecular Therapy - Oncolytics, Vol. 16, 27.03.2020, p. 289-301.

Research output: Contribution to journalArticlepeer-review

Harvard

Leung, EYL, Ennis, DP, Kennedy, PR, Hansell, C, Dowson, S, Farquharson, M, Spiliopoulou, P, Nautiyal, J, Mcnamara, S, Carlin, LM, Fisher, K, Davis, DM, Graham, G & Mcneish, IA 2020, 'NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer', Molecular Therapy - Oncolytics, vol. 16, pp. 289-301. https://doi.org/10.1016/j.omto.2020.02.001

APA

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., & Mcneish, I. A. (2020). NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer. Molecular Therapy - Oncolytics, 16, 289-301. https://doi.org/10.1016/j.omto.2020.02.001

Vancouver

Author

Leung, Elaine Y.l. ; Ennis, Darren P. ; Kennedy, Philippa R. ; Hansell, Christopher ; Dowson, Suzanne ; Farquharson, Malcolm ; Spiliopoulou, Pavlina ; Nautiyal, Jaya ; Mcnamara, Sophie ; Carlin, Leo M. ; Fisher, Kerry ; Davis, Daniel M. ; Graham, Gerard ; Mcneish, Iain A. / NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer. In: Molecular Therapy - Oncolytics. 2020 ; Vol. 16. pp. 289-301.

Bibtex

@article{864d88b0ce4e45aebd7b1018ef9be805,
title = "NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer",
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 dl922-947 (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 dl922-947 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.",
keywords = "DNAM-1TIGIT, Ovarian cancer, Oncolytic viru, Adenovirus, NK cell",
author = "Leung, {Elaine Y.l.} and Ennis, {Darren P.} and Kennedy, {Philippa R.} and Christopher Hansell and Suzanne Dowson and Malcolm Farquharson and Pavlina Spiliopoulou and Jaya Nautiyal and Sophie Mcnamara and Carlin, {Leo M.} and Kerry Fisher and Davis, {Daniel M.} and Gerard Graham and Mcneish, {Iain A.}",
year = "2020",
month = mar,
day = "27",
doi = "10.1016/j.omto.2020.02.001",
language = "English",
volume = "16",
pages = "289--301",
journal = "Molecular Therapy - Oncolytics",
issn = "2372-7705",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - NK cells augment oncolytic adenovirus cytotoxicity in ovarian cancer

AU - Leung, Elaine Y.l.

AU - Ennis, Darren P.

AU - Kennedy, Philippa R.

AU - Hansell, Christopher

AU - Dowson, Suzanne

AU - Farquharson, Malcolm

AU - Spiliopoulou, Pavlina

AU - Nautiyal, Jaya

AU - Mcnamara, Sophie

AU - Carlin, Leo M.

AU - Fisher, Kerry

AU - Davis, Daniel M.

AU - Graham, Gerard

AU - Mcneish, Iain A.

PY - 2020/3/27

Y1 - 2020/3/27

N2 - 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 dl922-947 (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 dl922-947 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.

AB - 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 dl922-947 (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 dl922-947 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.

KW - DNAM-1TIGIT

KW - Ovarian cancer

KW - Oncolytic viru

KW - Adenovirus

KW - NK cell

U2 - 10.1016/j.omto.2020.02.001

DO - 10.1016/j.omto.2020.02.001

M3 - Article

VL - 16

SP - 289

EP - 301

JO - Molecular Therapy - Oncolytics

JF - Molecular Therapy - Oncolytics

SN - 2372-7705

ER -