Adoptive Immunotherapy for Pancreatic Cancer Using MUC1 Peptide-pulsed Dendritic Cells and Activated T Lymphocytes

Background: Pancreatic cancer has a poor prognosis. The clinical efficacy of immunotherapy using both dendritic cells pulsed with MUC1 peptide (MUC1-DC) and, cytotoxic T lymphocyte (CTL) sensitized with a pancreatic cancer, YPK-1, expressing MUC1 (MUC1-CTL) was evaluated. Patients and Methods: Twenty patients with unresectable or recurrent pancreatic cancer were enrolled. Peripheral blood mononuclear cells (PBMCs) were separated into adherent cells for induction of MUC1-DCs and floating cells for MUC1-CTLs. MUC1-DCs were generated by culture with granulocyte monocyte colony stimulating factor (GM- CSF) and interleukin-4 (IL-4) and then exposed to MUC1 peptide and TNF-·. MUC1-CTLs were induced by co-culture with YPK-1 and then with interleukin-2 (IL-2). MUC1-DCs were injected intradermally and MUC1-CTLs were given intravenously. Results: Patients were treated from 2 to 15 times. One patient with multiple lung metastases experienced a complete response. Five patients had stable disease. The mean survival time was 9.8 months. No grade II-IV toxicity was observed. Conclusion: Adoptive immunotherapy with MUC1- DC and MUC1-CTL may be feasible and effective for pancreatic cancer. Pancreatic cancer has the poorest prognosis among gastrointestinal cancer because of its low resectability, malignant behavior and low sensitivity to anticancer agents (1). Treatments for pancreatic cancer, including surgery, chemotherapy and radiotherapy, have failed to improve the prognosis (2, 3). Eighty percent of patients are not eligible for surgical resection because of local spread or metastatic disease at the time of diagnosis. Even with curative surgery, the mean survival time (MST) does not exceed 2 years, with a 5-year survival of 15%-25% (4-6). New treatment strategies are necessary to improve the outcome of patients with pancreatic cancer. Immunotherapy has an advantage over radiation and