Dendritic Cell Immunotherapy for Ovarian Cancer: An Overview of Our Achievements

Abstract

Epithelial ovarian carcinoma (EOC) is the fifth leading cause of cancer-related death in women, largely reflecting the early dissemination of this malignant disease to the peritoneum. Due to its immunological features, EOC has poor response to immune checkpoint inhibitors (ICIs), including a limited tumor mutational burden (TMB), poor infiltration by immune cells, and active immunosuppression. Thus, novel strategies are needed to overcome the frequent lack of pre-existing immunity in patients with EOC. We developed and tested an autologous dendritic cell (DC)-based vaccine (DCVAC), which has recently been shown to be safe and to significantly improve progression-free survival (PFS) in two independent randomized phase II clinical trials enrolling patients with EOC (SOV01, NCT02107937; SOV02, NCT02107950). In addition, our exploratory data analyses suggest that the clinical benefits of the DCVAC were more pronounced in patients with EOC with lower-than-median TMBs and reduced CD8+ T cell infiltration. Thus, the DC-based vaccine stands out as a promising clinical tool to jumpstart anticancer immunity in patients with immunologically “cold” EOC. Our findings underscore the need for personalized immunotherapy and the clinical relevance of potential tumor-related biomarkers within the immunotherapy field. Additional clinical trials are needed to address these strategies as well as the potential value of the TMB and immune infiltration at baseline as biomarkers for guiding the clinical management of EOC.

Keywords

• ovarian cancer
• immunotherapy
• dendritic cells
• clinical trials