Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine.
BACKGROUND
Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer.


METHODS
MUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups.


RESULTS
The DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (P < 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (P < 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (P < 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells.


CONCLUSIONS
The MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer.
Rong
Yefei
Y
Department of General surgery, Zhongshan Hospital, Fudan University, Shanghai, PR China. mcyryf@163.com
Jin
Dayong
D
Wu
Wenchuan
W
Lou
Wenhui
W
Wang
Danshong
D
Kuang
Tiantao
T
Ni
Xiaoling
X
Qin
Xinyu
X
D000230:Adenocarcinoma / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D011897:Random Allocation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D020080:Tandem Repeat Sequences; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; C060192:MUC1 protein, human; D018396:Mucin-1; D019444:Vaccines, DNA