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

PMID: 31727154
Journal: Journal for immunotherapy of cancer (volume: 7, issue: 1, J Immunother Cancer 2019 Nov;7(1):302)
Published: 2019-11-14

Westdorp H, Creemers JHA, van Oort IM, Schreibelt G, Gorris MAJ, Mehra N, Simons M, de Goede AL, van Rossum MM, Croockewit AJ, Figdor CG, Witjes JA, Aarntzen EHJG, Mus RDM, Brüning M, Petry K, Gotthardt M, Barentsz JO, de Vries IJM, Gerritsen WR


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 Ga-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.