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

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.

• Authors: Reinhard Meier, Daniel Golovko, Sidhartha Tavri, Tobias D Henning, Christiane Knopp, Guido Piontek, Martina Rudelius, Petra Heinrich, Winfried S Wels, Heike Daldrup-Link
• Journal: Magnetic resonance in medicine (Magn Reson Med) Vol. 65 Issue 3 Pg. 756-63 (Mar 2011) ISSN: 1522-2594 [Electronic] United States
• PMID: 20928869 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 Wiley-Liss, Inc.

Topics

• Animals
• Cell Line, Tumor
• Cell Tracking (methods)
• Immunotherapy, Adoptive (methods)
• Killer Cells, Natural (pathology, transplantation)
• Magnetic Resonance Imaging (methods)
• Male
• Prognosis
• Prostatic Neoplasms (pathology, surgery)
• Rats
• Rats, Nude
• Staining and Labeling (methods)
• Treatment Outcome