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  • Interleukin-6-controlled, mesenchymal stem cell-based sodium/iodide symporter gene therapy improves survival of glioblastoma-bearing mice.

Interleukin-6-controlled, mesenchymal stem cell-based sodium/iodide symporter gene therapy improves survival of glioblastoma-bearing mice.

Molecular therapy oncolytics (2023-09-13)
Carolin Kitzberger, Khuram Shehzad, Volker Morath, Rebekka Spellerberg, Julius Ranke, Katja Steiger, Roland E Kälin, Gabriele Multhoff, Matthias Eiber, Franz Schilling, Rainer Glass, Wolfgang A Weber, Ernst Wagner, Peter J Nelson, Christine Spitzweg
ZUSAMMENFASSUNG

New treatment strategies are urgently needed for glioblastoma (GBM)-a tumor resistant to standard-of-care treatment with a high risk of recurrence and extremely poor prognosis. Based on their intrinsic tumor tropism, adoptively applied mesenchymal stem cells (MSCs) can be harnessed to deliver the theranostic sodium/iodide symporter (NIS) deep into the tumor microenvironment. Interleukin-6 (IL-6) is a multifunctional, highly expressed cytokine in the GBM microenvironment including recruited MSCs. MSCs engineered to drive NIS expression in response to IL-6 promoter activation offer the possibility of a new tumor-targeted gene therapy approach of GBM. Therefore, MSCs were stably transfected with an NIS-expressing plasmid controlled by the human IL-6 promoter (IL-6-NIS-MSCs) and systemically applied in mice carrying orthotopic GBM. Enhanced radiotracer uptake by 18F-Tetrafluoroborate-PET/magnetic resonance imaging (MRI) was detected in tumors after IL-6-NIS-MSC application as compared with mice that received wild-type MSCs. Ex vivo analysis of tumors and non-target organs showed tumor-specific NIS protein expression. Subsequent 131I therapy after IL-6-NIS-MSC application resulted in significantly delayed tumor growth assessed by MRI and improved median survival up to 60% of GBM-bearing mice as compared with controls. In conclusion, the application of MSC-mediated NIS gene therapy focusing on IL-6 biology-induced NIS transgene expression represents a promising approach for GBM treatment.

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Sigma-Aldrich
Anti-Natrium/Iodid-Symporter-Antikörper, AS 625–643, Klon FP5A, clone FP5A, Chemicon®, from mouse