Investigation of GM-CSF immune accessory effects in tumor-bearing mice by direct gene immunization

Immunol Invest. 2006;35(2):227-37. doi: 10.1080/08820130600634550.

Abstract

To assess GM-CSF immune accessory effects in tumor-bearing mice, an animal tumor model was established by inoculating SP2/0 myeloma cells s.c. into the flank of Balb/c mice and 14 days later, injecting either 400 mug recombinant pcDNA3.1/mGM-CSF or a blank plasmid s.c. or i.m. into the tumor four times. The tumor weight, the activities of CTL and NK, the serum levels of IFN-gamma, IL-2 and lymphocytes infiltrating in tumor tissue were analysed 8 weeks later with MTT, ELISA and pathological section methods. The results showed that the tumor lump was reduced in mice injected s.c. (0.880 +/- 0.405 g) or i.m. (0.378 +/- 0.411 g) with pcDNA3.1/mGM-CSF compared with control mice injected s.c. (1.548 +/- 0.221g, P < 0.01)or i.m. (1.554 +/- 0.249g, P < 0.001) with a blank vector. Lymphocyte infiltration in tumor tissues was very apparent in mice injected i.m. with pcDNA3.1/mGM-CSF. In contrast, there was no lymphocyte infiltration in tumor tissues of control mice. In addition, the serum concentrations of IFN-gamma, IL-2 and the activities of CTL and NK cells were significantly increased in mice injected with pcDNA3.1/mGM-CSF compared with a control mice (P < 0.01). In conclusion, direct gene immunization of recombinant pcDNA3.1/mGM-CSF is a feasible strategy for tumor therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Immunotherapy, Active / methods
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Killer Cells, Natural / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Mice, Inbred BALB C
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vaccines, DNA / pharmacology*

Substances

  • Cancer Vaccines
  • Interleukin-2
  • Vaccines, DNA
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor