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 - Adenovirus
KW - DNAM-1TIGIT
KW - NK cell
KW - Oncolytic viru
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85081210928&partnerID=8YFLogxK
U2 - 10.1016/j.omto.2020.02.001
DO - 10.1016/j.omto.2020.02.001
M3 - Article
SN - 2372-7705
VL - 16
SP - 289
EP - 301
JO - Molecular Therapy - Oncolytics
JF - Molecular Therapy - Oncolytics
ER -
