Journal Article

DKFZ-2023-00416

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model.

Koch, J. ; Beil, J.DKFZ* ; Berchtold, S. ; Mönch, D. ; Maaß, A. ; Smirnow, I. ; Schenk, A. ; Carter, M. E. ; Kloker, L. D. ; Leibold, T. ; Renner, P. ; Dahlke, M.-H. ; Lauer, U. M.DKFZ*

2023
MDPI Basel

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.

Keyword(s): ex vivo peritoneal culture model ; oncolytic measles vaccine virus ; oncolytic vaccinia virus ; peritoneal carcinomatosis ; virotherapy

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Contributing Institute(s):

1. DKTK TU zentral (TU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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