BACKGROUND: Dendritic cell (DC)-based immunotherapy is an emerging new treatment option in ovarian cancer, an important cause of cancer-related mortality. PATIENTS AND METHODS: One patient with ovarian carcinosarcoma (OCS) and one with serous ovarian cancer (SOC) received four weekly vaccinations of autologous DCs electroporated with mRNA coding for the Wilms' tumor gene 1 (WT1). Safety, feasibility and immunogenicity were assessed. RESULTS: Vaccination was feasible without toxicity. In an ex vivo antigen re-stimulation assay of peripheral blood mononuclear cells, both patients showed increasing cluster of differentiation 137 (CD137+) antigen-specific T-cells and interleukin 10 (IL-10) production post-vaccination. Moreover, interleukin-2 (IL-2) production increased (OCS) as well as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) (SOC). Disease in patients progressed after four vaccines and patients continued with conventional therapies. After cessation of immunotherapy, they had an extended survival of 19 (OCS) and 12 (SOC) months. CONCLUSION: To our knowledge, we report for the first time the feasibility and T-cell immunogenicity of WT1 mRNA-loaded DC immunotherapy in ovarian cancer.
BACKGROUND: Dendritic cell (DC)-based immunotherapy is an emerging new treatment option in ovarian cancer, an important cause of cancer-related mortality. PATIENTS AND METHODS: One patient with ovarian carcinosarcoma (OCS) and one with serous ovarian cancer (SOC) received four weekly vaccinations of autologous DCs electroporated with mRNA coding for the Wilms' tumor gene 1 (WT1). Safety, feasibility and immunogenicity were assessed. RESULTS: Vaccination was feasible without toxicity. In an ex vivo antigen re-stimulation assay of peripheral blood mononuclear cells, both patients showed increasing cluster of differentiation 137 (CD137+) antigen-specific T-cells and interleukin 10 (IL-10) production post-vaccination. Moreover, interleukin-2 (IL-2) production increased (OCS) as well as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) (SOC). Disease in patients progressed after four vaccines and patients continued with conventional therapies. After cessation of immunotherapy, they had an extended survival of 19 (OCS) and 12 (SOC) months. CONCLUSION: To our knowledge, we report for the first time the feasibility and T-cell immunogenicity of WT1 mRNA-loaded DC immunotherapy in ovarian cancer.
Entities:
Keywords:
DC immunotherapy; WT1; carcinosarcoma; ovarian cancer
Authors: Sterre T Paijens; Ninke Leffers; Toos Daemen; Wijnand Helfrich; H Marike Boezen; Ben J Cohlen; Cornelis Jm Melief; Marco de Bruyn; Hans W Nijman Journal: Cochrane Database Syst Rev Date: 2018-09-10
Authors: Galaxia M Rodriguez; Kristianne J C Galpin; Curtis W McCloskey; Barbara C Vanderhyden Journal: Cancers (Basel) Date: 2018-07-24 Impact factor: 6.639
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