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Immunological effects and viral gene expression determine the efficacy of oncolytic measles vaccines encoding IL-12 or IL-15 agonists

Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immun...

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Bibliographic Details
Main Authors: Backhaus, Paul S. (Author) , Poth, Tanja (Author) , Jäger, Dirk (Author) , Ungerechts, Guy (Author) , Engeland, Christine Elisabeth (Author)
Format: Article (Journal)
Language:English
Published: 3 October 2019
In: Viruses
Year: 2019, Volume: 11, Issue: 10, Pages: 914
ISSN:1999-4915
DOI:10.3390/v11100914
Online Access:Verlag, Volltext: https://doi.org/10.3390/v11100914
Verlag: https://www.mdpi.com/1999-4915/11/10/914
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Author Notes:Paul S. Backhaus, Rūta Veinalde, Laura Hartmann, Jessica E. Dunder, Lara M. Jeworowski, Jessica Albert, Birgit Hoyler, Tanja Poth, Dirk Jäger, Guy Ungerechts and Christine E. Engeland
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Summary:Tumor-targeted immunomodulation using oncolytic viral vectors is currently being investigated as a promising strategy in cancer therapy. In a previous study, we showed that a measles virus Schwarz vaccine strain (MeVac) vector encoding an interleukin-12 fusion protein (FmIL-12) is an effective immunotherapy in the MC38cea murine colon adenocarcinoma model. We hypothesized that MeVac encoding interleukin-15 may mediate enhanced T and NK cell responses and thus increase the therapeutic efficacy, especially in NK cell-controlled tumors. Therefore, we generated MeVac vectors encoding an interleukin-15 superagonist, FmIL-15. Replication and oncolytic capacity, transgene expression, and functionality of MeVac FmIL-15 vectors were validated in vitro. Effects on the tumor immune landscape and therapeutic efficacy of both FmIL-12 and FmIL-15 vectors were studied in the MC38cea and B16hCD46 tumor models. Treatment with MeVac FmIL-15 increased T and NK cell infiltration in both models. However, MeVac FmIL-12 showed more robust viral gene expression and immune activation, resulting in superior anti-tumor efficacy. Based on these results, MeVac encoding a human IL-12 fusion protein was developed for future clinical translation.
Item Description:Gesehen am 15.01.2020
Physical Description:Online Resource
ISSN:1999-4915
DOI:10.3390/v11100914

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