Establishment of dendritic cell vaccines targeting a tumor antigen, MUC1 and application for its clinical therapeutics for cancer.

使用树突状细胞（DC）进行癌症疫苗接种可有效抑制癌症进展。这是因为DC作为抗原呈递细胞在有效引发肿瘤特异性免疫中起关键作用。在这项研究中，我们分析了DC诱导肿瘤特异性免疫的能力和靶向MUC1肿瘤抗原的DC疫苗免疫治疗的临床效果。来自14名晚期或转移性乳腺癌或肺癌患者（9名MUC1阳性，5名MUC1阴性）的DC负载MUC1抗原或肿瘤裂解物，并用于治疗性疫苗接种。接种后，所有MUC1阳性患者均获得抗原特异性免疫，而只有一例MUC1阴性癌症患者显示特异性免疫。在临床上，9例MUC1阳性病例中有7例观察到显著效果，如肿瘤大小或肿瘤标志物水平降低或恶性胸腔积液消失。然而，MUC1阴性患者对DC疫苗没有反应，除了一例MAGE 3阳性肺癌患者。与MUC1阴性患者相比，MUC1阳性患者的生存期显著延长（平均生存期：16.75 vs 3.80个月，p= 0.0101）。这些数据表明MUC 1具有足够的免疫原性，可以作为肿瘤抗原引发强烈的抗肿瘤免疫，并且靶向MUC 1的DC疫苗可用于癌症的免疫治疗。

The use of dendritic cells (DCs) for cancer vaccination is effective in suppressing cancer progression. This is because the DCs play a crucial role in priming tumor-specific immunity efficiently as antigen-presenting cells. In this study, we analyzed the ability of DCs to elicit tumor-specific immunity and clinical effects of DC vaccine immunotherapy targeting MUC1 tumor antigens. DCs from 14 patients with advanced or metastatic breast or lung cancer (9 positive for MUC1 and 5 negative for MUC1) were loaded with MUC1 antigens or tumor lysate and used for therapeutic vaccination. After vaccination, all of the MUC1-positive patients acquired antigen-specific immunity whereas only one case with MUC1-negative cancer showed the specific immunity. Clinically, marked effects such as reduction in tumor sizes or tumor marker levels or disappearance of malignant pleural effusion were observed in 7 of the 9 MUC1-positive cases. However, MUC1-negative patients did not respond to DC vaccines, with the exception of one case with MAGE3-positive lung cancer. Survival of MUC1-positive patients was significantly prolonged in comparison with MUC1-negative patients (mean survival : 16.75 versus 3.80 months, p=.0101). These data suggest that MUC1 is sufficiently immunogenic to elicit strong anti-tumor immunity as a tumor antigen and that DC vaccines targeting MUC1 are useful for immunotherapy of cancer.