Dendritic cell-based vaccine prolongs survival and time to next therapy independently of the vaccine cell number

Abstract

AbstractIn 2009, new EU legislation regulating advanced therapy medicinal products (ATMPs), consisting of gene therapy, tissue engineering and cell-based medicines, was introduced. Although less than 20 ATMPs were authorized since that time, the awarding of the Nobel Prize for Physiology or Medicine in 2018 revived interest in developing new cancer immunotherapies involving significant manipulation of the patient's own immune cells, including lymphocytes and dendritic cells. The lymphocytes are mainly thought to directly affect tumour cells, dendritic cells are involved in indirect mechanisms by antigen presentation to other leukocytes orchestrating the immune response. It is the latter cells that are the focus of this brief review. Based on the recent results of our study treating patients with castration-resistant prostate cancer (CRPC) with an immunohybridoma cell construct (termed aHyC), produced by electrofusion of autologous tumour and dendritic cells, we compare their effectiveness with a matched documented control group of patients. The results revealed that cancer-specific survival and the time to next in-line therapy (TTNT) were both significantly prolonged versus controls. When patients were observed for longer periods since the time of diagnosis of CRPC, 20% of patients had not yet progressed to the next in-line therapy even though the time under observation was ~ 80 months. Interestingly, analysis of survival of patients revealed that the effectiveness of treatment was independent of the number of cells in the vaccine used for treatment. It is concluded that autologous dendritic cell-based immunotherapy is a new possibility to treat not only CRPC but also other solid tumours.