期刊
BRITISH JOURNAL OF CANCER
卷 109, 期 6, 页码 1488-1497出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.494
关键词
dendritic cells; prostate cancer vaccine; Concholepas haemocyanin; PSA; memory T cells; DTH
类别
资金
- National Fund for Scientific and Technological Development [FONDECYT 1130320 FS-O, 1130324 MNL, 3090044 LS]
- Fund for the Promotion of Scientific and Technological Development [FONDEF DO5I10366, D11I1036 FS-O]
- Millennium Science Initiative from the Ministry for the Economy, Development and Tourism [P09/016-F]
- National Commission for Scientific and Technological Research (CONICYT) [21061192, 24100211]
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.
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