A comparative study of gene vaccines encoding different extracellular domains of the vascular endothelial growth factor receptor 2 in the mouse model of colon adenocarcinoma CT-26

Cancer Biol Ther. 2008 Apr;7(4):502-9. doi: 10.4161/cbt.7.4.5477. Epub 2007 Jan 2.

Abstract

Aims: To compare the immunogenicity and anti-tumor effects of gene vaccines encoding domains 1-4 with full length of extracellular region of VEGFR2.

Results: Both DNA vaccines decreased VEGF levels and rose specific antibodies; the lymphocyte subsets of vaccinated mice maintained high; tumor latency period and survival time of immunized mice were prolonged; tumor size, weight, MVD and liver metastases were significantly less than the control groups.

Methods: Mouse model of CT-26 adenocarcinoma of colon were treated with orally immunized gene vaccine encoding extracellular 1-4 and full length of VEGFR2 respectively. The effect of anti-tumor was evaluated by detecting the tumor volume, mice survival time, intratumoral microvessel density (MVD) and liver metastases. To explore the reasonable mechanism of the oral gene vaccines, the levels of VEGF and anti-VEGFR2 antibody in serum were detected by ELISA, CD4+ and CD8+ T cells in peripheral blood and subcutaneous tumors were analyzed by flow cytometer and immunohischemistry respectively.

Conclusion: Compared with full length of extracellular domain of VEGFR2, extracellular regions 1-4 of VEGFR2 has been sufficient to decrease the serum VEGF level and to inhibit tumor growth and metastasis specifically.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / prevention & control
  • Adenocarcinoma / secondary
  • Administration, Oral
  • Animals
  • Antibodies / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Liver Neoplasms / prevention & control
  • Liver Neoplasms / secondary
  • Mice
  • Protein Structure, Tertiary / genetics
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / immunology

Substances

  • Antibodies
  • Cancer Vaccines
  • Vaccines, DNA
  • Vascular Endothelial Growth Factor Receptor-2