Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity

Cancer Immunol Immunother. 2016 Mar;65(3):327-39. doi: 10.1007/s00262-016-1796-7. Epub 2016 Feb 10.


Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase. Tumor antigen-specific T cell responses were monitored in blood and skin-test infiltrating-lymphocyte cultures. Almost all patients mounted prophylactic vaccine- or KLH-specific immune responses. Both after intranodal injection and after intradermal/intravenous injection, tumor antigen-specific immune responses were detected, which coincide with longer overall survival in stage IV melanoma patients. VAC-DC induce local and systemic CTC grade 2 and 3 toxicity, which is most likely caused by BCG in the maturation cocktail. The side effects were self-limiting or resolved upon a short period of systemic steroid therapy. We conclude that VAC-DC can induce functional tumor-specific responses. Unfortunately, toxicity observed after vaccination precludes the general application of VAC-DC, since in DC maturated with prophylactic vaccines BCG appears to be essential in the maturation cocktail.

Keywords: Dendritic cells; Immunotherapy; Maturation; Melanoma; Prophylactic vaccines; Toll-like receptor ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BCG Vaccine / immunology
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Dinoprostone / pharmacology
  • Female
  • Hemocyanins / immunology
  • Humans
  • Male
  • Melanoma / immunology
  • Melanoma / therapy*
  • Middle Aged
  • Monocytes / cytology*
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / immunology
  • T-Lymphocytes / immunology
  • Vaccination
  • gp100 Melanoma Antigen / genetics
  • gp100 Melanoma Antigen / immunology


  • BCG Vaccine
  • Cancer Vaccines
  • gp100 Melanoma Antigen
  • Hemocyanins
  • Monophenol Monooxygenase
  • keyhole-limpet hemocyanin
  • Dinoprostone