Comparative analysis of antigen loading strategies of dendritic cells for tumor immunotherapy

J Immunother. Jul-Aug 2004;27(4):265-72. doi: 10.1097/00002371-200407000-00002.

Abstract

Dendritic cells (DCs) loaded with antigens can effectively stimulate host immune responses to syngeneic tumors, but there is considerable controversy as to which forms of antigen-loading are most immunogenic. Here, the authors compared immunotherapeutic reactivities of DCs loaded with a variety of antigen preparations. Because DC maturation stages affect their capacities of antigen processing and presentation, two DC populations were used for the current analysis: in vivo Flt-3 ligand-induced mature DCs and in vitro bone marrow-derived DCs, which were less mature. To facilitate a direct comparison, the LacZ gene-transduced B16 melanoma model system was used, where beta-galactosidase served as the surrogate tumor-rejection antigen. DC loading strategies included pulsing with the beta-galactosidase protein, H-2K restricted peptide, tumor cell lysate, and irradiated tumor cells and fusion of DCs with tumor cells. Our results demonstrated that electrofusion of DCs and tumor cells generated a therapeutic vaccine far superior to other methods of DC loading. For the treatment of 3-day established pulmonary tumor nodules, a single intranodal vaccination plus IL-12 resulted in a significant reduction of metastatic nodules, while other DC preparations were only marginally effective. Immunotherapy mediated by the fusion cells was tumor antigen-specific. Consistent with their therapeutic activity, fusion hybrids were the most potent stimulators to induce specific IFN-gamma secretion from immune T cells. Furthermore, fusion cells also stimulated a small amount of IL-10 production from immune T cells. However, this IL-10 secretion was also induced by other DC preparations and did not correlate with in vivo therapeutic reactivity.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens / immunology*
  • Cancer Vaccines / immunology
  • Cell Fusion
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Female
  • Immunotherapy / methods*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • T-Lymphocytes / metabolism

Substances

  • Antigens
  • Cancer Vaccines
  • Interleukin-10
  • Interferon-gamma