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

Autor: Koch J; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.; University of Tübingen, 72074 Tübingen, Germany., Beil J; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tübingen, Germany., Berchtold S; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Mönch D; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.; University of Tübingen, 72074 Tübingen, Germany., Maaß A; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.; University of Tübingen, 72074 Tübingen, Germany., Smirnow I; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Schenk A; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Carter ME; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Kloker LD; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany., Leibold T; Department of General and Visceral Surgery, Robert Bosch Hospital, 70376 Stuttgart, Germany., Renner P; Department of General and Visceral Surgery, Robert Bosch Hospital, 70376 Stuttgart, Germany.; University Medical Centre Regensburg, 93053 Regensburg, Germany., Dahlke MH; Department of General and Visceral Surgery, Robert Bosch Hospital, 70376 Stuttgart, Germany., Lauer UM; Department of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 72076 Tübingen, Germany.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2023 Jan 27; Vol. 15 (2). Date of Electronic Publication: 2023 Jan 27.
DOI: 10.3390/v15020363
Abstrakt: 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: MEDLINE
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