TY  - JOUR
AU  - Koch, Jana
AU  - Beil, Julia
AU  - Berchtold, Susanne
AU  - Mönch, Dina
AU  - Maaß, Annika
AU  - Smirnow, Irina
AU  - Schenk, Andrea
AU  - Carter, Mary E
AU  - Kloker, Linus D
AU  - Leibold, Tobias
AU  - Renner, Philipp
AU  - Dahlke, Marc-H
AU  - Lauer, Ulrich M
TI  - Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model.
JO  - Viruses
VL  - 15
IS  - 2
SN  - 1999-4915
CY  - Basel
PB  - MDPI
M1  - DKFZ-2023-00416
SP  - 363
PY  - 2023
AB  - 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.
KW  - ex vivo peritoneal culture model (Other)
KW  - oncolytic measles vaccine virus (Other)
KW  - oncolytic vaccinia virus (Other)
KW  - peritoneal carcinomatosis (Other)
KW  - virotherapy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36851574
DO  - DOI:10.3390/v15020363
UR  - https://inrepo02.dkfz.de/record/272843
ER  -