Therapeutic vaccination against advanced pancreatic cancer by autologous dendritic cells pulsed with a MUC1 peptide: Preclinic..

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Author(s): D. Jin, Y. Rong, W. Lou, X. Qin, W. Wu, X. Nin, X. Nin, D. Wang, T. Kuang, Y. Qin; General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China; Biotherapy Center, Medical School of Shanghai, Shanghai, China



Background: Pancreatic ductal adenocarcinoma has a particularly poor prognosis. Therefore, novel therapeutic strategies such as immunotherapy are required. The aim of the present phase I study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) pulsed with a specific MUC1 peptide in advanced pancreatic cancer patients.


Methods: Five patients who had pancreatic cancer ductal adenocarcinoma expressing MUC1 in stage of III/IV were enrolled to the clinical trial. Patients underwent leukapheresis to generate dendritic cells by culture in vitro with granulocyte macrophage colony-stimulating factor and interleukin-4 for 5 days. Dendritic cells were then pulsed overnight with MUC1 peptide (GVTSAPDTRPAPGSTAPPAH) and harvested for vaccination. Dendritic cells (3×106-6×106) were injected intradermally every 2 weeks for 3-4 times.


Results: All patients remained with progressive disease. Four patients developed strong T-cell IFN-? and Granzyme B Elispot responses to the vaccine. Most interestingly, the patient who was treated with the highest number of DC(6×106) had more number of CTL than other patients and showed delayed-type hypersensitivity responses at injection sites and this patient stopped application of the analgetics. Another patient with relapsed pancreatic cancer who had finished the 4 times of vaccination and then followed 6 times of chemotherapy with Gemcitabine had a surprisingly long term of survival of 12 month. No evidence of significant treatment related toxicity or auto-immunity was observed.


Conclusions: This study showed the safety and clinical response of MUC1 peptide-pulsed dendritic cell therapy for patients with advanced pancreatic cancer. It confirms the capability of this DC vaccine to stimulate an immune response in patients with pancreatic cancer even in the presence of a large tumor burden. Dendritic cell therapy is recommended for further clinical studies in pancreatic cancer patients.