Ovarian cancer remains the deadliest gynecological malignancy, responsible for approximately 207,000 fatalities worldwide in 2020. The disease is often diagnosed at advanced stages, when it has spread beyond the ovaries, resulting in a poor prognosis and limited treatment options. The five-year survival rate for advanced ovarian cancer is approximately 30%. Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for several cancers, their impact on epithelial ovarian cancer (EOC) has been limited. However, emerging evidence suggests that cancer immunotherapy could hold promise for EOC.
This thesis of Vrouyr Bilemjian seeks to generate new insights into the mechanisms by how EOC evades the immune system and to identify novel therapeutic approaches. We have investigated potential immune checkpoints contributing to immune suppression in EOC, focusing on TIM-3 and the relatively unexplored GPR56. Additionally, we have explored the use of CD20 as a biomarker for identifying relevant subsets of tumor-infiltrating lymphocytes (TILs). To address the issue of 'on-target/off-tumor toxicity' associated with broadly active immunomodulatory drugs, we also examined targeted drug delivery strategies, to enhance therapeutic precision and minimize harm to healthy tissues. Specifically, we designed a novel type of tumor-specific antigen-selective polysaccharide nanoparticle, which shows promise as a delivery vehicle for treating various cancers.
By advancing understanding in these areas, this thesis aims to contribute to the development of more effective immunotherapies and targeted treatments for ovarian cancer.
