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Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model

Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due t...

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Autores principales: Koch, Jana, Beil, Julia, Berchtold, Susanne, Mönch, Dina, Maaß, Annika, Smirnow, Irina, Schenk, Andrea, Carter, Mary E., Kloker, Linus D., Leibold, Tobias, Renner, Philipp, Dahlke, Marc-H., Lauer, Ulrich M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963964/
https://www.ncbi.nlm.nih.gov/pubmed/36851574
http://dx.doi.org/10.3390/v15020363
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author Koch, Jana
Beil, Julia
Berchtold, Susanne
Mönch, Dina
Maaß, Annika
Smirnow, Irina
Schenk, Andrea
Carter, Mary E.
Kloker, Linus D.
Leibold, Tobias
Renner, Philipp
Dahlke, Marc-H.
Lauer, Ulrich M.
author_facet Koch, Jana
Beil, Julia
Berchtold, Susanne
Mönch, Dina
Maaß, Annika
Smirnow, Irina
Schenk, Andrea
Carter, Mary E.
Kloker, Linus D.
Leibold, Tobias
Renner, Philipp
Dahlke, Marc-H.
Lauer, Ulrich M.
author_sort Koch, Jana
collection PubMed
description Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models.
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spelling pubmed-99639642023-02-26 Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model Koch, Jana Beil, Julia Berchtold, Susanne Mönch, Dina Maaß, Annika Smirnow, Irina Schenk, Andrea Carter, Mary E. Kloker, Linus D. Leibold, Tobias Renner, Philipp Dahlke, Marc-H. Lauer, Ulrich M. Viruses Article Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models. MDPI 2023-01-27 /pmc/articles/PMC9963964/ /pubmed/36851574 http://dx.doi.org/10.3390/v15020363 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koch, Jana
Beil, Julia
Berchtold, Susanne
Mönch, Dina
Maaß, Annika
Smirnow, Irina
Schenk, Andrea
Carter, Mary E.
Kloker, Linus D.
Leibold, Tobias
Renner, Philipp
Dahlke, Marc-H.
Lauer, Ulrich M.
Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
title Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
title_full Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
title_fullStr Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
title_full_unstemmed Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
title_short Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
title_sort establishing a new platform to investigate the efficacy of oncolytic virotherapy in a human ex vivo peritoneal carcinomatosis model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963964/
https://www.ncbi.nlm.nih.gov/pubmed/36851574
http://dx.doi.org/10.3390/v15020363
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