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

Koch, Jana and Beil, Julia and Berchtold, Susanne and Moench, Dina and Maass, Annika and Smirnow, Irina and Schenk, Andrea and Carter, Mary E. E. and Kloker, Linus D. D. and Leibold, Tobias and Renner, Philipp and Dahlke, Marc-H. and Lauer, Ulrich M. M. (2023) Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model. VIRUSES-BASEL, 15 (2): 363. ISSN , 1999-4915

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: VIRUS; METASTASIS; peritoneal carcinomatosis; ex vivo peritoneal culture model; virotherapy; oncolytic measles vaccine virus; oncolytic vaccinia virus
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Mar 2024 06:15
Last Modified: 26 Mar 2024 06:15
URI: https://pred.uni-regensburg.de/id/eprint/60520

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