Data from Mesenchymal Stem Cell–mediated Image-guided Sodium Iodide Symporter (<i>NIS</i>) Gene Therapy Improves Survival of Glioblastoma-bearing Mice

Abstract

<div>AbstractPurpose:<p>Mesenchymal stem cells (MSC) have emerged as cellular-based vehicles for the delivery of therapeutic genes in cancer therapy based on their inherent tumor-homing capability. As theranostic gene, the sodium iodide symporter (<i>NIS)</i> represents a successful target for noninvasive radionuclide-based imaging and therapy. In this study, we applied genetically engineered MSCs for tumor-targeted <i>NIS</i> gene transfer in experimental glioblastoma (GBM)—a tumor with an extremely poor prognosis.</p>Experimental Design:<p>A syngeneic, immunocompetent GL261 GBM mouse model was established by subcutaneous and orthotopic implantation. Furthermore, a subcutaneous xenograft U87 model was used. Bone marrow–derived MSCs were stably transfected with a NIS-expressing plasmid driven by the constitutively active cytomegalovirus promoter (NIS-MSC). After multiple or single intravenous injection of NIS-MSCs, tumoral iodide uptake was monitored <i>in vivo</i> using <sup>123</sup>I-scintigraphy or <sup>124</sup>I-PET. Following validation of functional NIS expression, a therapy trial with <sup>131</sup>I was performed on the basis of the most optimal application regime as seen by <sup>124</sup>I-PET imaging in the orthotopic approach.</p>Results:<p>A robust tumoral NIS-specific radionuclide accumulation was observed after NIS-MSC and radioiodide application by NIS-mediated <i>in vivo</i> imaging. NIS immunofluorescence staining of GBM and non-target tissues showed tumor-selective MSC homing along with NIS expression. Application of therapeutically effective <sup>131</sup>I led to significantly delayed tumor growth and prolonged median survival after NIS-MSC treatment as compared with controls.</p>Conclusions:<p>A strong tumor-selective recruitment of systemically applied MSCs into GBM was found using <i>NIS</i> as reporter gene followed by successful therapeutic application of radioiodide demonstrating the potential use of <i>NIS</i>-based MSCs as therapy vehicles as a new GBM therapy approach.</p></div>