Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

BMC Cancer. 2009 Jun 18;9:191. doi: 10.1186/1471-2407-9-191.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / prevention & control
  • Adenocarcinoma / therapy
  • Animals
  • Antibodies, Neoplasm / blood
  • Antibodies, Neoplasm / immunology
  • Antibody Specificity
  • Blotting, Western
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Mucin-1 / genetics
  • Mucin-1 / immunology*
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / prevention & control
  • Pancreatic Neoplasms / therapy
  • Random Allocation
  • T-Lymphocytes, Cytotoxic / immunology
  • Tandem Repeat Sequences
  • Vaccines, DNA / immunology
  • Vaccines, DNA / pharmacology*

Substances

  • Antibodies, Neoplasm
  • Cancer Vaccines
  • MUC1 protein, human
  • Mucin-1
  • Vaccines, DNA