前列腺癌树突细胞瘤苗的制备及其应用

目的 构建前列腺癌树突细胞（DC）瘤苗，并探讨其体内外抗前列腺癌的作用。方法 分离C57BL／6小鼠骨髓前体细胞制备DC，光镜下观察DC的形态学特征，混合淋巴细胞试验、辣根过氧化物酶（HRP）吞噬试验观察DC的生物学特性。经RM-1前列腺癌细胞裂解产物致敏构建DC瘤苗，将DC瘤苗皮下注射于18只前列腺癌模型小鼠。结果成熟DC突起多而长，胞内囊泡少，刺激T细胞增殖能力强；DC瘤苗分泌IL-12能力增强；小鼠应用DC瘤苗后，其脾脏T细胞对RM-1细胞具有特异性杀伤作用；荷瘤小鼠肿瘤生长缓慢，坏死明显，瘤体内及肿瘤周围有大量炎细胞浸润。结论小鼠骨髓单核细胞在粒细胞／巨细胞集落刺激因子（GM-CSF）和IL-4诱导下可转化为DC。RM-1前列腺癌细胞裂解物致敏构建的DC瘤苗能诱导T细胞对RM-1细胞产生特异性杀伤作用，且能分泌更多的IL-12，可用于前列腺癌的免疫治疗。

Preparation and application of dendritc cell vaccine pulsed with RM-1 prostate cancer cell lysates

[Objective] To construct dendritic cell(DC) vaccine pulsed with RM-1 prostate cancer cell lysate,detect the specific anti-tumor activity of DC vaccine in vitro and vivo.[Methods] The C57BL/6 mouse bone marrow precursor cells were isolate and cultured with cytokines of GM-CSF and IL-4 to propagate DC.DC was pulsed with RM-1 prostate cancer cell lysate.18 prostate cancer model mice were injected subcutaneously with vaccine.The effect of inducing specific kill activity of DC vaccine was detected.The therapeutic effect of DC vaccine on mice with prostate cancer was assessed.[Results] Mature DC possessed long processes,and few of vacuoles in the cytoplasm.The proliferation activity of stimulating allogeneic T cell increased.DC vaccine pulsed with RM-1 cell lysate had stronger activity of secreting IL-12.The mice immunized with DC vaccine showed a specific CTL response.In the mice model with RM-1 prostate cancer,DC vaccine could inhibit tumor growth significantly.The survival time of the mice treated with DC vaccine was greatly prolonged.Histological examination showed that tumor necrosis and infiltration of inflammatory cells inside and around the tumors.[Conclusions] DC can be transformed from mouse bone marrow progenitors by culturing the cells with GM-CSF and IL-4.DC vaccine pulsed with RM-1 prostate cancer cell lysate can effectively induce CTL against RM-1 and have strong activity of secreting IL-12.DC vaccine can induce significant antitumor effects through efficient induction of specific immune responses.