Mesenchymal Stem Cell-mediated Image-guided Sodium Iodide Symporter (NIS) Gene Therapy Improves Survival of Glioblastoma-bearing Mice.

Autor:	Kitzberger C; Department of Internal Medicine IV, University Hospital, LMU Munich, Munich, Germany., Spellerberg R; Department of Internal Medicine IV, University Hospital, LMU Munich, Munich, Germany., Han Y; Department of Internal Medicine IV, University Hospital, LMU Munich, Munich, Germany., Schmohl KA; Department of Internal Medicine IV, University Hospital, LMU Munich, Munich, Germany., Stauss C; Department of Internal Medicine IV, University Hospital, LMU Munich, Munich, Germany., Zach C; Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany., Kälin RE; Neurosurgical Research, Department of Neurosurgery, University Hospital, LMU Munich, Munich, Germany.; Walter Brendel Center of Experimental Medicine, Faculty of Medicine, LMU Munich, Munich, Germany., Multhoff G; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Radiation Immuno-Oncology group, Munich, Germany.; Department of Radiation Oncology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Eiber M; Department of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Schilling F; Department of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Glass R; Neurosurgical Research, Department of Neurosurgery, University Hospital, LMU Munich, Munich, Germany.; Walter Brendel Center of Experimental Medicine, Faculty of Medicine, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), partner site Munich, Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany., Weber WA; Department of Nuclear Medicine, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Wagner E; Pharmaceutical Biotechnology, Department of Pharmacy, Centre for System-Based Drug Research and Centre for Nanoscience, LMU Munich, Munich, Germany., Nelson PJ; Department of Internal Medicine IV, University Hospital, LMU Munich, Munich, Germany., Spitzweg C; Department of Internal Medicine IV, University Hospital, LMU Munich, Munich, Germany.; Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Mar 01; Vol. 29 (5), pp. 930-942.
DOI:	10.1158/1078-0432.CCR-22-1433
Abstrakt:	Purpose: 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 (NIS) represents a successful target for noninvasive radionuclide-based imaging and therapy. In this study, we applied genetically engineered MSCs for tumor-targeted NIS gene transfer in experimental glioblastoma (GBM)-a tumor with an extremely poor prognosis. Experimental Design: 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 in vivo using 123I-scintigraphy or 124I-PET. Following validation of functional NIS expression, a therapy trial with 131I was performed on the basis of the most optimal application regime as seen by 124I-PET imaging in the orthotopic approach. Results: A robust tumoral NIS-specific radionuclide accumulation was observed after NIS-MSC and radioiodide application by NIS-mediated in vivo imaging. NIS immunofluorescence staining of GBM and non-target tissues showed tumor-selective MSC homing along with NIS expression. Application of therapeutically effective 131I led to significantly delayed tumor growth and prolonged median survival after NIS-MSC treatment as compared with controls. Conclusions: A strong tumor-selective recruitment of systemically applied MSCs into GBM was found using NIS as reporter gene followed by successful therapeutic application of radioiodide demonstrating the potential use of NIS-based MSCs as therapy vehicles as a new GBM therapy approach. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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