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

Authors: Harm Westdorp, Jeroen H. A. Creemers, Inge M. van Oort, Gerty Schreibelt, Mark A.J. Gorris, Niven Mehra, Michiel Simons, Anna L. de Goede, Michelle M. van Rossum, Alexandra Croockewit, Carl G. Figdor, J. Alfred Witjes, Erik H.J.G. Aarntzen, Roel Mus, Mareke Brüning, Katja Petry, Martin Gotthardt, Jelle O. Barentsz, I. Jolanda M. de Vries, Winald R. Gerritsen - Journal for ImmunoTherapy of Cancer 2019 cited by 113

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 68 Ga-prostate-specific membrane antigen PET/CT, according to RECIST 1.1, PCWG2 criteria and immune-related response criteria.