1. Modeling ovarian cancer for dendritic cells‐derived exosomes treatment

Abstract

Ovarian cancer (OC) is the fifth leading cause of death from cancer among women in the United States and high‐grade serous carcinoma (HGSC) is the most common subtype. Patients often present metastatic disease with ascites buildup, which further complicates the treatment landscape. Although immunotherapy is a promising cancer treatment method, it fails to have an impact on HGSC patients due to the immunosuppressive and heterogeneous micro‐environment and impaired lymphatic drainage created by cancer cells within the peritoneal cavity. We are interested in boosting the anti‐tumor immunity by employing exosomes derived from dendritic cells (DC)‐based vaccines (Dex) for their capacity of overcoming the transport barriers, bypassing the immunosuppressive environment, prompting T cell infiltration in target organs, and activating them. Dex were collected and characterized in terms of yield, size distribution, and their biomolecular features as compared to parental cells, proving the expression of MHC‐II and co‐stimulatory markers (CD80 and CD86). When DC were pulsed with tumor antigen lysates from an ovalbumin‐overexpressing cancer cell line (ID8‐OVA), Dex presented OVA on their surface and activated the proliferation of OVA‐specific T cells (OT‐I). Intra‐peritoneal injection of Dex into a metastatic OC mouse model revealed a preferential accumulation within the peritoneal metastatic nodules, in tumors and in the liver. Preliminary data suggest Dex as a potential complement to the standard of care treatments for metastatic OC. We are currently testing their ability to induce an anti‐tumor immune response and increase survival when coupled with standard chemotherapeutics, with the potential of being effective in several metastatic diseases with peritoneal invasion.