Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes
ABSTRACT
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-alpha. 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.