Dendritic cell immunotherapy in serous ovarian cancer.
Ovarian cancer is the second most important pelvic tumor with limited treatment options in case of relapsing tumors, leading to a poor prognosis. New therapies are needed. Earlier, we developed dendritic cell (DC) immunotherapy for uterine cancers, based on the tumorassociated antigen (TAA) Wilms’ tumor gene 1 (WT1). DCs were produced in the laboratory starting from regular white blood cells from a patient. These DCs were loaded with WT1 in its genetic form (RNA) and then re-injected into the patient, activating defender cells (T cells), which destroy WT1 positive tumor cells. Our first phase I/II trial was completed in 2012 and showed clinical response in 50% of patients. In the current research project, we will design a similar therapy for ovarian cancer with this difference that we will not use one TAA but a combination of tumor lysate together with 3 defined TAAs, mainly to avoid tumor escape. In vitro stimulation experiments to explore this strategy are aimed to support a first clinical trial. The combination of tumor lysate-loaded DCs and DCs loaded with specific TAAs is innovative in the field of immunotherapy. The latter DCs will allow TAA-specific immunomonitoring approaches. For the immunomonitoring of lysate-loaded DCs, we will develop a whole blood culture methodology which will allow us to analyze tumor antigenresponding cells and a mixture of cytokines. With this project, we hope to create a new therapeutic option for relapsing ovarian cancer patients.