My Master’s project focuses on re-arming patients’ own Natural Killer (NK) cells as a second-line therapy for ovarian cancer. Ovarian cancer is the most deadly gynecological cancer as the majority of women with the disease do not survive 5 years. Annually, there is an estimated loss of 29,600 potential years of life for women in Canada due to ovarian cancer. For such poor prognosis cancers, new, effective therapies are needed.
The growing field of cancer immunotherapy aims to harness the inherent ability of immune cells to fight cancer. In healthy individuals, Natural Killer (NK) immune cells have an intrinsic ability to distinguish and eliminate malignant cells and thus play a critical role in the body’s defense against cancer. However, cancer patient NK cells have diminished anti-tumour activity. Recently, the adoptive transfer of NK cells to patients has shown clinical success in treating hematological malignancies. However, their ability to treat solid tumours has been limited due to an inability to maintain NK cell function in the immunosuppressive tumour environment. While empowering a patient’s own (autologous) NK cells is an attractive immunotherapeutic approach, the impaired function of NK cells from cancer patients needs to be overcome. Furthermore, contrary to cytotoxic peripheral blood NK cells, NK cells in the immunosuppressive tumour environment, such as ascites in the case of ovarian cancer, exhibit pro-tumourigenic functions and phenotype.
My project looks to overcome the limitations of autologous NK cell therapy against solid malignancies by re-arming ovarian cancer patients’ own peripheral blood- and tumour-associated ascites fluid-NK cells through expansion. Using a patient-derived xenograft model of human ovarian cancer established in our lab, we assess the therapeutic effects of adoptively transferring patients’ own expanded NK cells in a translational model of the patient’s own ovarian cancer. If NK cell function in the tumour microenvironment can be improved, NK cell therapy against solid malignancies may experience similar success as with hematological malignancies.
My undergraduate thesis project in the lab consisted of studying a powerful method of NK cell activation with combined IL-18, IL-15, and IL-12 cytokine stimulation. Given the potent activation of NK cells, this method of stimulation has been explored for cancer immunotherapies. This stimulation is known to induce the production of high levels of the anti-tumour cytokine IFN-γ. My project focused on the mechanism of regulation of NK cell cytokine production following stimulation and uncovered that NK cells also produce high levels of IL-8 in response to IL-18/IL-15/IL-12 stimulation.
Financial support provided by the Ontario Women's Health Scholars Award.