Interleukin-6-controlled, mesenchymal stem cell-based sodium/iodide symporter gene therapy improves survival of glioblastoma-bearing mice
© 2023 The Authors..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Molecular therapy oncolytics - 30(2023) vom: 21. Sept., Seite 238-253 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kitzberger, Carolin [VerfasserIn] |
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| Links: |
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| Themen: |
Gene therapy |
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| Anmerkungen: |
Date Revised 14.09.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.omto.2023.08.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361991827 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a NIS | |
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| 650 | 4 | |a gene therapy | |
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| 650 | 4 | |a sodium/iodide symporter | |
| 700 | 1 | |a Shehzad, Khuram |e verfasserin |4 aut | |
| 700 | 1 | |a Morath, Volker |e verfasserin |4 aut | |
| 700 | 1 | |a Spellerberg, Rebekka |e verfasserin |4 aut | |
| 700 | 1 | |a Ranke, Julius |e verfasserin |4 aut | |
| 700 | 1 | |a Steiger, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Kälin, Roland E |e verfasserin |4 aut | |
| 700 | 1 | |a Multhoff, Gabriele |e verfasserin |4 aut | |
| 700 | 1 | |a Eiber, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Schilling, Franz |e verfasserin |4 aut | |
| 700 | 1 | |a Glass, Rainer |e verfasserin |4 aut | |
| 700 | 1 | |a Weber, Wolfgang A |e verfasserin |4 aut | |
| 700 | 1 | |a Wagner, Ernst |e verfasserin |4 aut | |
| 700 | 1 | |a Nelson, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Spitzweg, Christine |e verfasserin |4 aut | |
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