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
 
Abstract:
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.