Under the supervision of established investigator Dr. Julian Lum, this research project will focus on advancing immunotherapies for epithelial ovarian cancer. Previously, the Lum laboratory conducted a metabolomic analysis of samples obtained from patients with high-grade serous ovarian cancer to identify the metabolic interactions between distinct cell types across ascites and tumor environments. This led to the discovery of an ovarian tumour-derived metabolite, 1-methylnicotinamide (MNA), which shows potent immune suppressive activity. Their work revealed that MNA inhibits the efficacy of chimeric antigen receptor T (CAR-T) cell treatment of ovarian cancer cells.

The current research proposal aims to overcome the impact of this ovarian tumor-derived metabolite in CAR-T cells, to improve the response to immune therapy. As the metabolite MNA was found in ovarian cancer patients, all in vitro and in vivo experiments are conducted using human ovarian cancer cell lines.