| |  Online-Ressource |
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| Verfasst von: | Singh, Hans Martin [VerfasserIn]  |
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| | Leber, Mathias Felix [VerfasserIn] |
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| | Bossow, Sascha [VerfasserIn] |
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| | Engeland, Christine Elisabeth [VerfasserIn] |
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| | Dessila, Jan [VerfasserIn] |
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| | Großardt, Christian [VerfasserIn] |
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| | Plath, Karim [VerfasserIn] |
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| | Bell, John C. [VerfasserIn] |
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| | Jäger, Dirk [VerfasserIn] |
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| | Kalle, Christof von [VerfasserIn] |
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| | Ungerechts, Guy [VerfasserIn] |
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| Titel: | MicroRNA-sensitive oncolytic measles virus for chemovirotherapy of pancreatic cancer |
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| Verf.angabe: | Hans Martin Singh, Mathias Felix Leber, Sascha Bossow, Christine E. Engeland, Jan Dessila, Christian Grossardt, Karim Zaoui, John C. Bell, Dirk Jäger, Christof von Kalle and Guy Ungerechts |
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| E-Jahr: | 2021 |
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| Jahr: | 25 June 2021 |
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| Umfang: | 16 S. |
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| Fussnoten: | Gesehen am 04.03.2022 |
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| Titel Quelle: | Enthalten in: Molecular therapy. Oncolytics |
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| Ort Quelle: | London : Nature Publishing Group, 2014 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 21(2021), Seite 340-355 |
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| ISSN Quelle: | 2372-7705 |
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| Abstract: | Advanced pancreatic cancer is characterized by few treatment options and poor outcomes. Oncolytic virotherapy and chemotherapy involve complementary pharmacodynamics and could synergize to improve therapeutic efficacy. Likewise, multimodality treatment may cause additional toxicity, and new agents have to be safe. Balancing both aims, we generated an oncolytic measles virus for 5-fluorouracil-based chemovirotherapy of pancreatic cancer with enhanced tumor specificity through microRNA-regulated vector tropism. The resulting vector encodes a bacterial prodrug convertase, cytosine deaminase-uracil phosphoribosyl transferase, and carries synthetic miR-148a target sites in the viral F gene. Combination of the armed and targeted virus with 5-fluorocytosine, a prodrug of 5-fluorouracil, resulted in cytotoxicity toward both infected and bystander pancreatic cancer cells. In pancreatic cancer xenografts, a single intratumoral injection of the virus induced robust in vivo expression of prodrug convertase. Based on intratumoral transgene expression kinetics, we devised a chemovirotherapy regimen to assess treatment efficacy. Concerted multimodality treatment with intratumoral virus and systemic prodrug administration delayed tumor growth and prolonged survival of xenograft-bearing mice. Our results demonstrate that 5-fluorouracil-based chemovirotherapy with microRNA-sensitive measles virus is an effective strategy against pancreatic cancer at a favorable therapeutic index that warrants future clinical translation. |
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| DOI: | doi:10.1016/j.omto.2021.04.015 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.omto.2021.04.015 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S2372770521000656 |
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| | DOI: https://doi.org/10.1016/j.omto.2021.04.015 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | chemovirotherapy |
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| | cytosine deaminase |
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| | fluorouracil |
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| | measles virus |
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| | microRNAs |
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| | miR-148a |
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| | oncolytic viruses |
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| | pancreatic cancer |
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| | prodrugs |
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| | virotherapy |
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| K10plus-PPN: | 1794702148 |
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| Verknüpfungen: | → Zeitschrift |
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MicroRNA-sensitive oncolytic measles virus for chemovirotherapy of pancreatic cancer / Singh, Hans Martin [VerfasserIn]; 25 June 2021 (Online-Ressource)
