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Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus

First-line treatment of recurrent and/or refractory head and neck squamous cell carcinoma (HNSCC) is based on platinum, 5-fluorouracil (5-FU) and the monoclonal antiEGFR antibody cetuximab. However, in most cases this chemoimmunotherapy does not cure the disease, and more than 50% of HNSCC patients...

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Hauptverfasser: Plath, Karim (VerfasserIn) , Bossow, Sascha (VerfasserIn) , Großardt, Christian (VerfasserIn) , Leber, Mathias Felix (VerfasserIn) , Springfeld, Christoph (VerfasserIn) , Plinkert, Peter K. (VerfasserIn) , Kalle, Christof von (VerfasserIn) , Ungerechts, Guy (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2012
In: Cancer gene therapy
Year: 2012, Jahrgang: 19, Heft: 3, Pages: 181-191
ISSN:1476-5500
DOI:10.1038/cgt.2011.75
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1038/cgt.2011.75
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/cgt201175
Volltext
Verfasserangaben:K. Zaoui, S. Bossow, C. Grossardt, M. F. Leber, C. Springfeld, P. K. Plinkert, C. von Kalle and G. Ungerechts
Beschreibung
Zusammenfassung:First-line treatment of recurrent and/or refractory head and neck squamous cell carcinoma (HNSCC) is based on platinum, 5-fluorouracil (5-FU) and the monoclonal antiEGFR antibody cetuximab. However, in most cases this chemoimmunotherapy does not cure the disease, and more than 50% of HNSCC patients are dying because of local recurrence of the tumors. In the majority of cases, HNSCC overexpress the epidermal growth factor receptor (EGFR), and its presence is associated with a poor outcome. In this study, we engineered an EGFR-targeted oncolytic measles virus (MV), armed with the bifunctional enzyme cytosine deaminase/uracil phosphoribosyltransferase (CD/UPRT). CD/UPRT converts 5-fluorocytosine (5-FC) into the chemotherapeutic 5-FU, a mainstay of HNSCC chemotherapy. This virus efficiently replicates in and lyses primary HNSCC cells in vitro. Arming with CD/UPRT mediates efficient prodrug activation with high bystander killing of non-infected tumor cells. In mice bearing primary HNSCC xenografts, intratumoral administration of MV-antiEGFR resulted in statistically significant tumor growth delay and prolongation of survival. Importantly, combination with 5-FC is superior to virus-only treatment leading to significant tumor growth inhibition. Thus, chemovirotherapy with EGFR-targeted and CD/UPRT-armed MV is highly efficacious in preclinical settings with direct translational implications for a planned Phase I clinical trial of MV for locoregional treatment of HNSCC.
Beschreibung:Published online 11 November 2011
Gesehen am 22.08.2018
Beschreibung:Online Resource
ISSN:1476-5500
DOI:10.1038/cgt.2011.75

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