Ovarian cancer is typically diagnosed at advanced stages and consequently has poor clinical outcomes. Standard of care is surgical debulking followed by chemotherapy; while many patients initially respond to treatment, 20-30% of patients are resistant to the chemotherapy, as indicated by recurrence within six months of completing treatment. Various immune-based therapies are being explored as alternative therapies for ovarian cancer, including natural killer cells, chimeric antigen receptor T cells, and dendritic cell vaccines. However, these approaches require extensive <i>ex vivo</i>manipulation and expansion of cells. The combination of <i>in vivo </i>focal ablation of solid tumors with immune checkpoint blockade has shown promise in establishing an antigen-specific cytotoxic T cell response. As ovarian cancer is typically detected after it has spread throughout the abdominal cavity, ablation of the primary tumor is likely insufficient for establishing a therapeutically relevant response. To that end, we have developed biomaterials to achieve ablation of metastatic ovarian cancer cells. One such approach involves addition of metal components to polymeric biomaterial scaffolds that have previously been shown to recruit metastatic cells in order to facilitate non-invasive thermal ablation of infiltrating cells in the abdominal cavity. While this approach would be suitable for patients with disseminating tumor cells circulating throughout the abdominal cavity that can be captured by the scaffold, for patients with extensive metastatic nodules already established throughout the abdomen, we instead sought to deliver a biomaterial to those metastatic sites to facilitate ablation. To that end, we have also developed graphene-based biomaterials that bind to ovarian cancer spheroids. Incorporation of a sonosensitizer within the biomaterial enables killing of attached tumor cells via ultrasound treatment. Current efforts are focused on evaluating the immune response following ablation for both approaches and identifying strategies for local or systemic immune modulation to promote a robust cytotoxic T cell response.

Biomaterial approaches for treatment of metastatic ovarian cancer

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.