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Depicting adoptive immunotherapy for prostate cancer in an animal model with magnetic resonance imaging.

Authors
  • Meier, Reinhard
  • Golovko, Daniel
  • Tavri, Sidhartha
  • Henning, Tobias D
  • Knopp, Christiane
  • Piontek, Guido
  • Rudelius, Martina
  • Heinrich, Petra
  • Wels, Winfried S
  • Daldrup-Link, Heike
Type
Published Article
Journal
Magnetic Resonance in Medicine
Publisher
Wiley (John Wiley & Sons)
Publication Date
Mar 01, 2011
Volume
65
Issue
3
Pages
756–763
Identifiers
DOI: 10.1002/mrm.22652
PMID: 20928869
Source
Medline
License
Unknown

Abstract

Genetically modified natural killer (NK) cells that recognize tumor-associated surface antigens have recently shown promise as a novel approach for cancer immunotherapy. To determine NK cell therapy response early, a real-time, noninvasive method to quantify NK cell homing to the tumor is desirable. The purpose of this study was to evaluate if MR imaging could provide a noninvasive, in vivo diagnosis of NK cell accumulation in epithelial cell adhesion molecule (EpCAM)-positive prostate cancers in a rat xenograft model. Genetically engineered NK-92-scFv(MOC31)-ζ cells, which express a chimeric antigen receptor specific to the tumor-associated EpCAM antigen, and nontargeted NK-92 cells were labeled with superparamagnetic particles of iron-oxides (SPIO) ferumoxides. Twelve athymic rats with implanted EpCAM positive DU145 prostate cancers received intravenous injections of 1.5×10(7) SPIO labeled NK-92 and NK-92-scFv(MOC31)-ζ cells. EpCAM-positive prostate cancers demonstrated a progressive and a significant decline in contrast-to-noise-ratio data at 1 and 24 h after injection of SPIO-labeled NK-92-scFv(MOC31)-ζ cells. Conversely, tumor contrast-to-noise-ratio data did not change significantly after injection of SPIO-labeled parental NK-92 cells. Histopathology confirmed an accumulation of the genetically engineered NK-92-scFv(MOC31)-ζ cells in prostate cancers. Thus, the presence or absence of a tumor accumulation of therapeutic NK cells can be monitored with cellular MR imaging. EpCAM-directed, SPIO labeled NK-92-scFv(MOC31)-ζ cells accumulate in EpCAM-positive prostate cancers.

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