Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model

Exp Dermatol. 2006 Nov;15(11):865-74. doi: 10.1111/j.1600-0625.2006.00479.x.


Mesenchymal stem cells (MSCs) represent a new tool for delivery of therapeutic agents to tumor cells. In this study, we have evaluated the anti-tumor activity of human MSCs stably transduced with a retroviral vector expressing the cytokine interleukin-12 (IL-12) in a mouse melanoma model. Application of MSC(IL-12) but not control MSCs strongly reduced the formation of lung metastases of B16F10 melanoma cells. The activity of the MSC(IL-12) cells was dependent on the presence of natural killer (NK) cells in this experimental setting. Further, MSC(IL-12) cells elicited a pronounced retardation of tumor growth and led to prolonged survival when injected into established subcutaneous melanoma in a therapeutic regimen. The therapeutic effect of the MSC(IL-12) was in part mediated by CD8(+) T cells, while NK cells and CD4(+) T cells appeared to play a minor role. The anti-tumor effect of MSC(IL-12) cells was of similar efficiency as observed for application of naked plasmid DNA encoding IL-12. The presented data demonstrate that these two different strategies can induce a similar therapeutic anti-tumor efficacy in the mouse melanoma tumor model.

MeSH terms

  • Animals
  • Biopsy
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Survival
  • Cells, Cultured
  • Disease Models, Animal
  • Humans
  • Immunophenotyping
  • Immunotherapy / methods*
  • Interferon-gamma / immunology
  • Interleukin-12 / genetics*
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy*
  • Melanoma / immunology
  • Melanoma / secondary
  • Melanoma / therapy*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Rats
  • Retroviridae / genetics
  • Spleen / cytology
  • Transduction, Genetic


  • Interleukin-12
  • Interferon-gamma