Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
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 t...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/15/2/363 |
| _version_ | 1797617794226847744 |
|---|---|
| author | Jana Koch Julia Beil Susanne Berchtold Dina Mönch Annika Maaß Irina Smirnow Andrea Schenk Mary E. Carter Linus D. Kloker Tobias Leibold Philipp Renner Marc-H. Dahlke Ulrich M. Lauer |
| author_facet | Jana Koch Julia Beil Susanne Berchtold Dina Mönch Annika Maaß Irina Smirnow Andrea Schenk Mary E. Carter Linus D. Kloker Tobias Leibold Philipp Renner Marc-H. Dahlke Ulrich M. Lauer |
| author_sort | Jana Koch |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T08:00:50Z |
| format | Article |
| id | doaj.art-822e82baacc441038ab92e364129dec5 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T08:00:50Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-822e82baacc441038ab92e364129dec52023-11-16T23:47:57ZengMDPI AGViruses1999-49152023-01-0115236310.3390/v15020363Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis ModelJana Koch0Julia Beil1Susanne Berchtold2Dina Mönch3Annika Maaß4Irina Smirnow5Andrea Schenk6Mary E. Carter7Linus D. Kloker8Tobias Leibold9Philipp Renner10Marc-H. Dahlke11Ulrich M. Lauer12Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDepartment of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, GermanyDepartment of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDepartment of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, GermanyDepartment of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, GermanyDepartment of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, GermanyDepartment of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, GermanyDepartment of General and Visceral Surgery, Robert Bosch Hospital, 70376 Stuttgart, GermanyDepartment of General and Visceral Surgery, Robert Bosch Hospital, 70376 Stuttgart, GermanyDepartment of General and Visceral Surgery, Robert Bosch Hospital, 70376 Stuttgart, GermanyDepartment of Medical Oncology and Pneumology, Virotherapy Center Tübingen (VCT), Medical University Hospital, 72076 Tübingen, GermanyOncolytic 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.https://www.mdpi.com/1999-4915/15/2/363peritoneal carcinomatosisex vivo peritoneal culture modelvirotherapyoncolytic measles vaccine virusoncolytic vaccinia virus |
| spellingShingle | Jana Koch Julia Beil Susanne Berchtold Dina Mönch Annika Maaß Irina Smirnow Andrea Schenk Mary E. Carter Linus D. Kloker Tobias Leibold Philipp Renner Marc-H. Dahlke Ulrich M. Lauer Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model Viruses peritoneal carcinomatosis ex vivo peritoneal culture model virotherapy oncolytic measles vaccine virus oncolytic vaccinia virus |
| title | Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model |
| title_full | Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model |
| title_fullStr | Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model |
| title_full_unstemmed | Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model |
| title_short | Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model |
| title_sort | establishing a new platform to investigate the efficacy of oncolytic virotherapy in a human ex vivo peritoneal carcinomatosis model |
| topic | peritoneal carcinomatosis ex vivo peritoneal culture model virotherapy oncolytic measles vaccine virus oncolytic vaccinia virus |
| url | https://www.mdpi.com/1999-4915/15/2/363 |
| work_keys_str_mv | AT janakoch establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT juliabeil establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT susanneberchtold establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT dinamonch establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT annikamaaß establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT irinasmirnow establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT andreaschenk establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT maryecarter establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT linusdkloker establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT tobiasleibold establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT philipprenner establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT marchdahlke establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel AT ulrichmlauer establishinganewplatformtoinvestigatetheefficacyofoncolyticvirotherapyinahumanexvivoperitonealcarcinomatosismodel |