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

被引:2
作者
Koch, Jana [1 ,2 ]
Beil, Julia [3 ,4 ]
Berchtold, Susanne [3 ]
Moench, Dina [1 ,2 ]
Maass, Annika [1 ,2 ]
Smirnow, Irina [3 ]
Schenk, Andrea [3 ]
Carter, Mary E. E. [3 ]
Kloker, Linus D. D. [3 ]
Leibold, Tobias [5 ]
Renner, Philipp [5 ,6 ]
Dahlke, Marc-H. [5 ]
Lauer, Ulrich M. M. [3 ,4 ]
机构
[1] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany
[2] Univ Tubingen, D-72074 Tubingen, Germany
[3] Med Univ Hosp, Virotherapy Ctr Tubingen VCT, Dept Med Oncol & Pneumol, D-72076 Tubingen, Germany
[4] German Canc Res Ctr, German Canc Consortium DKTK, D-72076 Tubingen, Germany
[5] Robert Bosch Krankenhaus, Dept Gen & Visceral Surg, D-70376 Stuttgart, Germany
[6] Univ Med Ctr Regensburg, D-93053 Regensburg, Germany
来源
VIRUSES-BASEL | 2023年 / 15卷 / 02期
关键词
peritoneal carcinomatosis; ex vivo peritoneal culture model; virotherapy; oncolytic measles vaccine virus; oncolytic vaccinia virus; VIRUS; METASTASIS;
D O I
10.3390/v15020363
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:18
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