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

Autor: Jana Koch, Julia Beil, Susanne Berchtold, Dina Mönch, Annika Maaß, Irina Smirnow, Andrea Schenk, Mary E. Carter, Linus D. Kloker, Tobias Leibold, Philipp Renner, Marc-H. Dahlke, Ulrich M. Lauer
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Viruses, Vol 15, Iss 2, p 363 (2023)
Druh dokumentu: article
ISSN: 15020363
1999-4915
DOI: 10.3390/v15020363
Popis: 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.
Databáze: Directory of Open Access Journals
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