Tumour cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients

Abstract

Background:Recently, we produced a tumour antigen-presenting cells (TAPCells) vaccine using a melanoma cell lysate, called TRIMEL, as an antigen source and an activation factor. Tumour antigen-presenting cells induced immunological responses and increased melanoma patient survival. Herein, we investigated the effect of TAPCells loaded with prostate cancer cell lysates (PCCL) as an antigen source, and TRIMEL as a dendritic cell (DC) activation factor; which were co-injected with the Concholepas concholepas haemocyanin (CCH) as an adjuvant on castration-resistant prostate cancer (CRPC) patients.Methods:The lysate mix capacity, for inducing T-cell activation, was analysed by flow cytometry and Elispot. Delayed-type hypersensitivity (DTH) reaction against PCCL, frequency of CD8+ memory T cells (Tm) in blood and prostate-specific antigen (PSA) levels in serum were measured in treated patients.Results:The lysate mix induced functional mature DCs that were capable of activating PCCL-specific T cells. No relevant adverse reactions were observed. Six out of 14 patients showed a significant decrease in levels of PSA. DTH+ patients showed a prolonged PSA doubling-time after treatment. Expansion of functional central and effector CD8+ Tm were detected.Conclusion:Treatment of CRPC patients with lysate-loaded TAPCells and CCH as an adjuvant is safe: generating biochemical and memory immune responses. However, the limited number of cases requires confirmation in a phase II clinical trial.

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer

“…This heat shock consists of exposing the cells to temperatures of 42 °C for a period of 1 hour and then 2 hours at physiological temperature (37 °C). Our data indicate that this conditioning of tumor cells from which the lysate is produced triggers danger signals that are essential to activate DCs and enhance antitumor signals to TL (Aguilera et al, 2011;Tittarelli et al, 2012;Reyes et al, 2013).…”

“…During the past 10 years, interaction between basic immunologists, clinicians and oncologists has facilitated a major international contribution to basic immunology and the development of cancer immunotherapy by our research group Escobar et al, 2005;López et al, 2006;Salazar-Onfray et al, 2008;López et al, 2009;Aguilera et al, 2011;Tittarelli et al, 2012;Durán et al, 2012;Reyes et al, 2013).…”

“…By obtaining monocytes, a population of very common cells taken from the patient's blood, we were able, through cell culture techniques and the use of cytokines and the aforementioned TRIMEL, to prepare antigen-presenting cells in about 48 hours (López et al, 2009;Aguilera et al, 2011). These cells are then subjected to an additional cell activation process, which allows obtaining DCs with increased potency for induction of an anti-tumor immune response in patients (López et al, 2009;Aguilera et al, 2011;Reyes et al, 2013). This in itself is a great advantage over other methods that use precursors from DCs obtained from blood, because the majority of these methods take 5-9 days to generate a suffi cient number of these cells.…”

“…Accordingly, using the international experience and our own scientifi c advances, we decided in 2003 to start phase I and II clinical trials, funded by the National Research and Development Agency FONDEF and approved by the Bioethics Committee for human studies of the Faculty of Medicine and the Clinical Hospital of the University of Chile. In these studies, TAPCells pulsed or loaded with allogeneic tumor lysates were used, as reported, in advanced melanoma and castration-resistant prostate cancer patients (Escobar et al, 2005;López et al, 2009;Aguilera et al, 2011;Reyes et al, 2013). An essential part of this process is the use of TRIMEL allogeneic cell lysate (López et al, 2009;Aguilera et al, 2011).…”

“…TRIMEL has been characterized from an antigenic point of view, demonstrating the presence of most of the melanomaassociated antigens currently described (López et al, 2009;Aguilera et al, 2011). Additionally, it has been shown that TRIMEL is capable of inducing the maturation of DCs in the absence of pro-infl ammatory cytokines such as TNF-α or IFN-α, and without the necessity of additional stimulus (Aguilera et al, 2011;Reyes et al, 2013). This tumor lysate can then act not only as a source of antigen for DCs, but also as an inducer of their activation.…”