New approaches in dendritic cell vaccination design and efficacy tests for patients with advanced ovarian cancer: Prospects for a phase I clinical study.

Abstract

TPS158 Background: Ovarian cancer can be characterized by initial responsiveness to surgery and chemotherapy followed by high recurrence and mortality rates. Vaccination with autologous dendritic cells offers a treatment option that may delay or even prevent recurrent and metastatic disease. In this study, three substantial immunological novelties are introduced to improve monitoring and clinical results of the dendritic cell based vaccination: 1) Autologous dendritic cells are loaded with two tumor associated antigens (TAAs) via two different pathways to elicit in parallel CD4+ and CD8+ T cells. 2) This is the first time loaded peptides can be verified directly on the surface of the dendritic cells. 3) A method is proposed to quantify cycling tumor cells (CTCs) in peripheral blood as diagnostic marker specific for ovarian cancer. Methods: 20 patients with advanced ovarian cancer will be enrolled eight weeks after standard treatment (surgery and chemotherapy). Each patient will be vaccinated intradermally on a weekly or fortnightly basis with 6×106 double loaded autologous mature dendritic cells. Autologous dendritic cells are loaded with two universal TAAs: TERT-mRNA and Survivin-peptide. Evidence of presentation of loaded petides in corresponding MHC complexes on the surface of the cells is provided by confocal fluorescence microscopy images. The primary objective of the study is to investigate the safety and tolerability of the active investigated autologous dendritic cell vaccine. The secondary objective of the study is to collect preliminary information of additional clinical and non-clinical parameters about the efficacy of the investigated immunotherapy in terms of expression of specific tumor markers, survival rate, time-to-progression and monitoring of CTCs specific for ovarian cancer. Results of peptide presentation via the two pathways in MHC complexes on dendritic cell surface and preliminary data of CTC analysis specific for ovarian cancer will be presented. No significant financial relationships to disclose.