Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer

J Immunother Cancer. 2019 Nov 14;7(1):302. doi: 10.1186/s40425-019-0787-6.


Background: Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC). We investigated the immunological response and clinical outcome of vaccination with blood-derived CD1c+ myeloid dendritic cells (mDCs; cDC2) and plasmacytoid DCs (pDCs).

Methods: In this randomized phase IIa trial, 21 chemo-naive CRPC patients received maximally 9 vaccinations with mature mDCs, pDCs or a combination of mDCs plus pDCs. DCs were stimulated with protamine/mRNA and loaded with tumor-associated antigens NY-ESO-1, MAGE-C2 and MUC1. Primary endpoint was the immunological response after DC vaccination, which was monitored in peripheral blood and in T cell cultures of biopsies of post-treatment delayed-type hypersensitivity-skin tests. Main secondary endpoints were safety, feasibility, radiological PFS (rPFS) and overall survival. Radiological responses were assessed by MRIs and contrast-enhanced 68Ga-prostate-specific membrane antigen PET/CT, according to RECIST 1.1, PCWG2 criteria and immune-related response criteria.

Results: Both tetramer/dextramer-positive (dm+) and IFN-γ-producing (IFN-γ+) antigen specific T cells were detected more frequently in skin biopsies of patients with radiological non-progressive disease (5/13 patients; 38%) compared to patients with progressive disease (0/8 patients; 0%). In these patients with vaccination enhanced dm+ and IFN-γ+ antigen-specific T cells median rPFS was 18.8 months (n = 5) vs. 5.1 months (n = 16) in patients without IFN-γ-producing antigen-specific T cells (p = 0.02). The overall median rPFS was 9.5 months. All DC vaccines were well tolerated with grade 1-2 toxicity.

Conclusions: Immunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome.

Trial registration: identifier NCT02692976, registered 26 February 2016, retrospectively registered.

Keywords: Castration-resistant prostate cancer; Dendritic cell vaccination; Immunotherapy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines*
  • Dendritic Cells / immunology*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / immunology
  • Middle Aged
  • Mucin-1 / immunology
  • Neoplasm Proteins / immunology
  • Prostatic Neoplasms, Castration-Resistant / immunology
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / therapy*
  • Skin / immunology
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Vaccination / adverse effects


  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • MAGEC2 protein, human
  • MUC1 protein, human
  • Membrane Proteins
  • Mucin-1
  • Neoplasm Proteins

Associated data