Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial

Cancer Immunol Immunother. 2020 Mar;69(3):477-488. doi: 10.1007/s00262-019-02466-x. Epub 2020 Jan 24.

Abstract

Background: Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination.

Methods: This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival.

Results: Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8+ T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences.

Conclusions: Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.

Keywords: Cisplatin; Dendritic cell; Immunotherapy; Melanoma; Vaccination.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cancer Vaccines / pharmacology
  • Cancer Vaccines / therapeutic use*
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Dendritic Cells / immunology*
  • Female
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Monocytes / immunology
  • Neoplasm Staging
  • Prospective Studies
  • Vaccination
  • Young Adult

Substances

  • Cancer Vaccines
  • Cisplatin