Dendritic cell vaccine immunotherapy of cancer targeting MUC1 mucin

Abstract

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 the MUC1-positive patients acquired antigen-specific immunity whereas only 1 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 1 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=0.0101). 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.