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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Bibliographic Details
Published in:Viruses 2023-01, Vol.15 (2), p.363
Main Authors: 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
Format: Article
Language:English
Subjects:
Abdominal cancer
Biological models
Care and treatment
Cell culture
Cell Death
Coculture Techniques
Colorectal cancer
ex vivo peritoneal culture model
Gastric cancer
Gene expression
Humans
Immunohistochemistry
Immunostimulation
Immunotherapy
Infections
Kinases
Lysis
Measles
Oncolysis
oncolytic measles vaccine virus
oncolytic vaccinia virus
Oncolytic Virotherapy
Oncolytic Viruses - genetics
peritoneal carcinomatosis
Peritoneal Neoplasms - therapy
Peritoneum
Proteins
Stainless steel
Tumor cell lines
Vaccines
virotherapy
Viruses
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Summary: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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v15020363