TY - JOUR
T1 - Tumour cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients
AU - Reyes, D.
AU - Salazar, L.
AU - Espinoza, E.
AU - Pereda, C.
AU - Castellón, E.
AU - Valdevenito, R.
AU - Huidobro, C.
AU - Inés Becker, M.
AU - Lladser, A.
AU - López, M. N.
AU - Salazar-Onfray, F.
N1 - Funding Information:
This study was supported by grants from the National Fund for Scientific and Technological Development (FONDECYT 1130320 FS-O, 1130324 MNL and 3090044 LS), the Fund for the Promotion of Scientific and Technological Development (FONDEF DO5I10366 and D11I1036 FS-O and MNL) and the Millennium Science Initiative from the Ministry for the Economy, Development and Tourism (P09/016-F). DR was supported by fellowships 21061192 and 24100211 of the National Commission for Scientific and Technological Research (CONICYT).
PY - 2013/9/17
Y1 - 2013/9/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84884592216&partnerID=8YFLogxK
U2 - 10.1038/bjc.2013.494
DO - 10.1038/bjc.2013.494
M3 - Article
C2 - 23989944
AN - SCOPUS:84884592216
SN - 0007-0920
VL - 109
SP - 1488
EP - 1497
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 6
ER -
