Cellular MRI as a suitable, sensitive non-invasive modality for correlating in vivo migratory efficiencies of different dendritic cell populations with subsequent immunological outcomes

Int Immunol. 2012 Jan;24(1):29-41. doi: 10.1093/intimm/dxr095. Epub 2011 Dec 20.

Abstract

The clinical application of dendritic cells (DC) as adjuvants in immunotherapies such as the cell-based cancer vaccine continues to gain interest. The overall efficacy of this emerging immunotherapy, however, remains low. Studies suggest the stage of maturation and activation of ex vivo-prepared DC immediately prior to patient administration is critical to subsequent DC migration in vivo, which ultimately affects overall vaccine efficacy. While it is possible to generate mature and activated DC ex vivo using various stimulatory cocktails, in the case of cancer patients, the qualitative and quantitative assessment of which DC stimulatory cocktail works most effectively to enhance subsequent DC migration in vivo is difficult. Thus, a non-invasive imaging modality capable of monitoring the real-time migration of DC in long-term studies is required. In this paper, we address whether cellular magnetic resonance imaging (MRI) is sufficiently sensitive to quantitatively detect differences in the migratory abilities of two different DC preparations: untreated (resting) versus ex vivo matured in a mouse model. In order to distinguish our ex vivo-generated DC of interest from surrounding tissues in magnetic resonance (MR) images, DC were labeled in vitro with the superparamagnetic iron oxide (SPIO) nanoparticle FeREX®. Characterization of DC phenotype and function following addition of a cytokine maturation cocktail and the toll-like receptor ligand CpG, both in the presence and in the absence of SPIO, were also carried out. Conventional histological techniques were used to verify the quantitative data obtained from MR images. This study provides important information relevant to tracking the in vivo migration of ex vivo-prepared and stimulated DC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • Cancer Vaccines / immunology
  • Cell Movement / immunology*
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Ferric Compounds / chemistry
  • Flow Cytometry
  • Humans
  • Immunotherapy / methods
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Oligodeoxyribonucleotides / immunology
  • Oligodeoxyribonucleotides / metabolism
  • Oligodeoxyribonucleotides / pharmacology
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Reproducibility of Results
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism

Substances

  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Cancer Vaccines
  • Cytokines
  • Ferric Compounds
  • OVA-8
  • Oligodeoxyribonucleotides
  • Peptide Fragments
  • Toll-Like Receptor 9
  • ferric oxide
  • Ovalbumin