Survival of castration‐resistant prostate cancer patients treated with dendritic–tumor cell hybridomas is negatively correlated with changes in peripheral blood CD56 bright CD16 − natural killer cells

Abstract

We investigated the clinical outcome of treating castration-resistant prostate cancer (CRPC) patients with autologous immunohybridoma cell (aHyC) vaccine generated by electrofusing autologous dendritic (DC) and tumor cells (TC), and tested whether the immunological response, involving the CD56 bright CD16 − natural killer (NK), putative pro-metastatic cells, 1,2 correlates with survival of CRPC patients. The results demonstrated that aHyC treatment is safe and prolongs patient survival correlating with a decrease in peripheral blood CD56 bright CD16 − NK cells. Despite advances in cancer immunotherapy, the only approved CRPC immunotherapy to date is a cell-based vaccine (sipuleucel-T), 3 with a single antigen-specific response induction mechanism, consisting of a small fraction of DC markers. DCs are able to activate both naive and memory T cells, ideally suited for augmenting antitu-mor immune responses. 4 Consistent with this, vaccination with enriched blood-derived DCs loaded with three tumor-associated antigens resulted in more frequent detection of antigen-specific T cells in CRPC patients. 5 Here, whole TCs were electrofused with DCs to produce aHyC vaccine. 6 The advantage of such hybrido-mas is their capacity of presenting both known and yet unknown tumor-associated antigens to T-lymphocytes. We used aHyC vaccine to treat chemotherapy-naive CRPC patients in a phase 1/2 randomized, placebo-controlled crossover trial to test primary outcomes-feasibility, safety, and quality of life (QL)-and also to evaluate clinical and immunological outcomes with overall survival (OS). Twenty-two men with CRPC were included (Table S1, Figure S1); 19 of them were treated with all four doses of the aHyC vaccine, either in first (aHyC-first group, n = 12) or in the second (placebo-first group, n = 10) trial session. Both This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.