The Establishment of Dendritic Cell-Tumor Fusion Vaccines for Hormone Refractory Prostate Cancer Cell

Abstract

Purpose: Dendritic cell (DC)-based tumor vaccine is an attractive modality for the treatment of hormone-refractory prostate cancer (HRPC) because it has some efficacy and few side effects in patients with poor general conditions. The aim of this study was to establish which is the most effective DC vaccine for the treatment of HRPC. We compared DC vaccine sensitized with tumor lysate and a fusion vaccine of DCs and tumor cells. Materials and Methods:The DU145 cancer cell line was purchased from the American Type Culture Collection. DCs were cultured from peripheral blood monocytes. Peripheral blood monocytes were cultured in RPMI 1640 medium supplemented with interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor, and 10% fetal calf serum. Tumor necrosis factor-alpha was added on day 7 to support maturation. Functional activity was measured in three groups: the DC single-culture group, the DC culture group with DC vaccine sensitized with tumor lysates, and the DC culture group prepared with tumor fusion vaccine made from irradiated tumor cells and monocyte-derived DCs by the polyethylene glycol method. Results: By FACS analysis, the rate of DC-tumor fusion vaccine was 20.3±3%. The IL-12 level produced by the DC-tumor fusion vaccine was significantly higher than that of DCs pulsed with tumor lysate (p＜0.05). Also, the generation of interferon-γ by tumor-specific T cells in the DC-tumor fusion vaccine group was superior to that of DCs pulsed with tumor lysate (p＜0.05). In addition, the T cells of the tumor lysate-pulsed DCs and tumor fusion vaccine had 1.6 and 2.5 times the functional activity, respectively, of the DC single-culture group in killing tumor cells in the cytotoxicity assay. Conclusions: The DC-tumor fusion vaccine seems to be more effective than DC single-culture or DC-tumor lysate vaccine in the treatment of HRPC.

Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?

“…Although CCs used in whole CC vaccines are often irradiated prior to use 19,26,27 and irradiation is able to cause ICD, 28 we cannot assume the antitumoral effects of these vaccines arise from immunogenically killed CCs. Indeed, the question remains whether irradiation can specifically and efficiently induce ICD.…”

“…8 The immunogenicity of whole CCs in vaccines can be increased through ICD. 19 In analogy, vaccines based on DCs pulsed with apoptotic cells are considered superior to those pulsed with whole cell lysate or necrotic cells. 18,20 ICD can be induced by chemical agents such as anthracyclines (e.g.…”

“…As a result, antigen presenting cells are stimulated to efficiently take up and process tumor antigens and cross-prime T cells. 19 In this article, we examined the in vivo effects of vaccines based on immunogenically killed CCs, induced by MTX, and whether the protective anticancer effects could be augmented through association with DCs (co-incubated or fused with these immunogenically killed CCs).…”

Regulation of Tumor Immunity by Tumor/Dendritic Cell Fusions

“…More importantly, in preclinical studies the fusions were also effective to induce CTL responses in vitro using colorectal [25, 97–102], gastric [103, 104], pancreatic [105], breast [43, 106–110], laryngeal [111], ovarian [34, 44, 112], lung [113], prostate [114, 115], renal [116, 117], and hepatocellular [118–120] carcinoma, leukemia [121–126], myeloma [127, 128] sarcoma [129, 130], melanoma [29, 131–133], glioma [124], and plasmacytoma [134]. …”

“…Tumor/DC fusions have been strongly effective in animal studies using melanoma [ 26 , 31 , 31 , 47 – 52 ], colorectal [ 18 , 30 , 45 , 50 , 51 , 53 – 59 ], breast [ 60 – 65 ], esophageal [ 66 ], pancreatic [ 67 , 68 ], hepatocellular [ 69 – 73 ], lung [ 74 – 78 ], renal cell carcinoma [ 79 ], sarcoma [ 80 – 85 ], myeloma [ 86 – 93 ], mastocytoma [ 94 ], lymphoma [ 95 ], and neuroblastoma [ 96 ]. More importantly, in preclinical studies the fusions were also effective to induce CTL responses in vitro using colorectal [ 25 , 97 – 102 ], gastric [ 103 , 104 ], pancreatic [ 105 ], breast [ 43 , 106 – 110 ], laryngeal [ 111 ], ovarian [ 34 , 44 , 112 ], lung [ 113 ], prostate [ 114 , 115 ], renal [ 116 , 117 ], and hepatocellular [ 118 – 120 ] carcinoma, leukemia [ 121 – 126 ], myeloma [ 127 , 128 ] sarcoma [ 129 , 130 ], melanoma [ 29 , 131 – 133 ], glioma [ 124 ], and plasmacytoma [ 134 ].…”