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.


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.


CONCLUSIONS
Adoptive immunotherapy with MUC1-DC and MUC1-CTL may be feasible and effective for pancreatic cancer.
Kondo
Hiroshi
H
Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Hazama
Shoichi
S
Kawaoka
Toru
T
Yoshino
Shigefumi
S
Yoshida
Shin
S
Tokuno
Kazuhisa
K
Takashima
Motonari
M
Ueno
Tomio
T
Hinoda
Yuji
Y
Oka
Masaaki
M
D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C060192:MUC1 protein, human; D018396:Mucin-1