Control of human mesothelin-expressing tumors by DNA vaccines

Gene Ther. 2007 Aug;14(16):1189-98. doi: 10.1038/sj.gt.3302974. Epub 2007 Jun 21.

Abstract

Mesothelin has been implicated as a potential ideal target antigen for the development of antigen-specific cancer immunotherapy for the control of mesothelin-expressing cancers such as ovarian cancer, mesothelioma and pancreatic adenocarcinoma. In the current study, we utilized a DNA vaccine encoding human mesothelin (pcDNA3-Hmeso) to treat C57BL/6 mice challenged with luciferase-expressing, Hmeso-expressing ovarian cancer cell line, Defb29 Vegf-luc/Hmeso. The therapeutic effect of the tumor-challenged mice was followed by noninvasive bioluminescence imaging systems. The mechanism of the antitumor effect was characterized by depletion of subsets of lymphocytes as well as adopted transfer of serum from pcDNA3-Hmeso-vaccinated mice. We found that vaccination with pcDNA3-Hmeso DNA vaccine generates a significant antitumor effect and promotes survival in mice challenged with Defb29 Vegf-luc/Hmeso. Furthermore, we found CD4+ and CD8+ T-cell immune responses as well as the humoral immune responses are important for the observed antitumor effects in vaccinated mice. Our data indicated that vaccination with DNA vaccine targeting Hmeso could generate potent antitumor effects against mesothelin-expressing tumors through both T cell-mediated immunity as well as antibody-mediated immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage*
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins
  • Genetic Therapy / methods*
  • Humans
  • Immunotherapy, Active / methods*
  • Killer Cells, Natural / immunology
  • Lymphocyte Depletion
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy*
  • Transfection / methods
  • Vaccines, DNA / administration & dosage*

Substances

  • Antibodies, Neoplasm
  • Cancer Vaccines
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • Vaccines, DNA
  • mesothelin