Tumour antigen-loaded mouse dendritic cells maturing in the presence of inflammatory cytokines are potent activators of immune response in vitro but not in vivo

Oncol Rep. 2009 Jun;21(6):1539-49. doi: 10.3892/or_00000386.

Abstract

The use of dendritic cells (DCs) loaded with tumour antigen is one of the most promising approaches to induce tumour-specific immune response. However, methods of the vaccine preparation have not yet been standardized. The purpose of the study was to analyse the anti-tumour efficacy of tumour antigen-loaded mouse bone marrow-derived dendritic cells (BM-DC/TAg) at different maturation stages. BM-DCs were loaded with MC38 colon carcinoma cell lysate (TAg) alone, to become partially differentiated, or were additionally stimulated with inflammatory cytokines such as TNF-alpha, IFN-gamma, or IL-12 to reach complete maturity. BM-DCs simultaneously stimulated with TAg and cytokines (especially IL-12 or IFN-gamma+IL-12) were in vitro more effective immune response activators than BM-DC/TAg cells. However, the highest anti-tumour effect in vivo was noted when mice were treated just with BM-DC/TAg. In a further study, the ability of IL-12 gene transduced BM-DCs (BM-DC/IL-12) to augment the immune response induced by BM-DC/TAg cells at different stages of maturation was examined. The highest anti-tumour effect was observed when partially differentiated BM-DC/TAg cells were injected simultaneously with BM-DC/IL-12 cells. The results suggest that partially differentiated BM-DC/TAg cells are more potent in evoking a strong anti-tumour response in vivo than mature BM-DCs. Moreover, the capacity of BM-DC/TAg cells for further differentiation and their sensitivity to factors secreted in vivo by the host or cells engineered to cytokine production seem to be of great importance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cells, Cultured
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Immunotherapy, Adoptive*
  • Inflammation Mediators / metabolism*
  • Interferon-gamma / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Spleen / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Time Factors
  • Transduction, Genetic
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Cytokines
  • Inflammation Mediators
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma