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NK Cells Augment Oncolytic Adenovirus Cytotoxicity in Ovarian Cancer

Elaine Y L Leung1,2, Darren P Ennis1,3, Philippa R Kennedy4

  • 1Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.

Molecular Therapy Oncolytics
|March 21, 2020
PubMed

Insights

Natural killer (NK) cells enhance oncolytic adenovirus (OV) therapy in ovarian cancer. Blocking the TIGIT receptor on NK cells may boost OV anti-cancer efficacy.

Area of Science:

  • Immunology
  • Virology
  • Oncology

Background:

  • Oncolytic viruses (OVs) elicit immune responses that can modulate their anti-cancer activity.
  • Natural killer (NK) cells are crucial for anti-viral and anti-tumoral immunity, but their role in oncolytic adenovirus (OV) therapy remains unexplored.

Purpose of the Study:

  • To investigate the impact of NK cells on the efficacy of two distinct oncolytic adenoviruses in ovarian cancer.
  • To determine if NK cells potentiate or inhibit OV anti-cancer activity.

Main Methods:

  • Utilized two oncolytic adenoviruses: Ad5 E1A CR2-deletion mutant dl922-947 and chimeric Ad3/Ad11p mutant enadenotucirev.
  • Employed primary human NK cells from peripheral blood and ovarian cancer ascites.
  • Assessed NK cell interaction with adenovirus-infected ovarian cancer cells and the influence of NK receptors DNAM-1 and TIGIT.

Main Results:

  • Oncolytic adenoviruses dl922-947 and enadenotucirev do not infect NK cells.
  • OVs induce contact-dependent activation of NK cells, leading to enhanced anti-cancer cytotoxicity against infected ovarian cancer cells.
  • Modulation of NK receptors DNAM-1 and TIGIT significantly affected NK cell cytotoxicity.

Conclusions:

  • NK cells enhance the anti-cancer efficacy of oncolytic adenoviruses in ovarian cancer.
  • Blocking the inhibitory NK receptor TIGIT presents a potential strategy to augment NK cell activity and improve OV therapeutic outcomes.
Keywords:
AdenovirusDNAM-1NK cellOncolytic virusOvarian cancerTIGIT

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