Natural Killer cells and oncolytic adenovirus therapy in ovarian cancer. (360G-Wellcome-102746_Z_13_Z)

Epithelial ovarian cancer is an immunogenic disease. Oncolytic viruses (OVs) are a new class of anti-cancer agent that generates potent innate and adaptive immune responses, which may influence clinical efficacy. NK cells are CD3- immune cells that play key roles in combating viral infection with the ability to lyse malignant cell and modulate adaptive immune responses. Further development of OVs will require understanding of their interactions with the host immune system. This research ai ms to assess the specific role of NK cells in the activity of oncolytic adenovirus in ovarian cancer. Hypothesis: NK cells within the peritoneal cavity attenuate the efficacy of OVs in ovarian cancer. Key goals: 1. To investigate the pattern of NK cell ligand and cytokine expression in human and murine ovarian cancer cells and these change following OV infection by flow cytometry, immunoblot, qRT-PCR and Luminex multiplex immunoassays. 2. To investigate NK cell composition in ovarian ca ncer ascites by flow cytometry and cytokine production by Luminex. 3. To investigate how NK cells influence the efficacy of oncolytic adenovirus through co-culture (NK cell lines and primary ascites cells with autologous NK cells) and in vivo xenograft experiments.