Immunological response after WT1 mRNA-loaded dendritic cell immunotherapy in ovarian carcinoma and carcinosarcoma

Anticancer Res. 2013 Sep;33(9):3855-9.

Abstract

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.

Keywords: DC immunotherapy; WT1; carcinosarcoma; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinosarcoma / immunology
  • Carcinosarcoma / metabolism
  • Carcinosarcoma / therapy*
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Electroporation
  • Female
  • Humans
  • Immunotherapy*
  • Middle Aged
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy*
  • RNA, Messenger / genetics*
  • Survival Analysis
  • WT1 Proteins / genetics*

Substances

  • Cytokines
  • RNA, Messenger
  • WT1 Proteins
  • WT1 protein, human