Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance. Oncolytic viruses have emerged as a new treatment approach and convey their antitumor activity through lysis of cancer cells. The therapeutic efficacy of oncolytic viruses is la...
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MDPI AG
2023-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/2/283 |
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| author | Selas T. F. Bots Sanne L. Landman Martijn J. W. E. Rabelink Diana J. M. van den Wollenberg Rob C. Hoeben |
| author_facet | Selas T. F. Bots Sanne L. Landman Martijn J. W. E. Rabelink Diana J. M. van den Wollenberg Rob C. Hoeben |
| author_sort | Selas T. F. Bots |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance. Oncolytic viruses have emerged as a new treatment approach and convey their antitumor activity through lysis of cancer cells. The therapeutic efficacy of oncolytic viruses is largely dependent on the induction of immunogenic cell death (ICD) and the subsequent antitumor immune responses. However, the concurrent generation of antiviral immune responses may also limit the a virus’ therapeutic window. GoraVir is a new oncolytic adenovirus derived from the Human Adenovirus B (HAdV-B) isolate AdV-lumc007 which was isolated from a gorilla and has demonstrated excellent lytic activity in both in vitro and in vivo models of PDAC. In this study, we characterized the immunostimulatory profile of cancer cell death induced by GoraVir and the concerted cellular antiviral responses in three conventional pancreatic cancer cell lines. While GoraVir was shown to induce late apoptotic/necrotic cell death at earlier time points post infection than the human adenovirus type 5 (HAdV-C5), similar levels of ICD markers were expressed. Moreover, GoraVir was shown to induce ICD not dependent on STING expression and regardless of subsequent antiviral responses. Together, these data demonstrate that GoraVir is an excellent candidate for use in oncolytic virotherapy. |
| first_indexed | 2024-03-11T08:00:20Z |
| format | Article |
| id | doaj.art-0a5f255e52f8489daa3b8340a31a7155 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T08:00:20Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-0a5f255e52f8489daa3b8340a31a71552023-11-16T23:46:55ZengMDPI AGViruses1999-49152023-01-0115228310.3390/v15020283Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer CellsSelas T. F. Bots0Sanne L. Landman1Martijn J. W. E. Rabelink2Diana J. M. van den Wollenberg3Rob C. Hoeben4Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The NetherlandsDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, The NetherlandsPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance. Oncolytic viruses have emerged as a new treatment approach and convey their antitumor activity through lysis of cancer cells. The therapeutic efficacy of oncolytic viruses is largely dependent on the induction of immunogenic cell death (ICD) and the subsequent antitumor immune responses. However, the concurrent generation of antiviral immune responses may also limit the a virus’ therapeutic window. GoraVir is a new oncolytic adenovirus derived from the Human Adenovirus B (HAdV-B) isolate AdV-lumc007 which was isolated from a gorilla and has demonstrated excellent lytic activity in both in vitro and in vivo models of PDAC. In this study, we characterized the immunostimulatory profile of cancer cell death induced by GoraVir and the concerted cellular antiviral responses in three conventional pancreatic cancer cell lines. While GoraVir was shown to induce late apoptotic/necrotic cell death at earlier time points post infection than the human adenovirus type 5 (HAdV-C5), similar levels of ICD markers were expressed. Moreover, GoraVir was shown to induce ICD not dependent on STING expression and regardless of subsequent antiviral responses. Together, these data demonstrate that GoraVir is an excellent candidate for use in oncolytic virotherapy.https://www.mdpi.com/1999-4915/15/2/283pancreatic ductal adenocarcinomaoncolytic virusnon-human primate adenovirusimmunogenic cell deathSTING |
| spellingShingle | Selas T. F. Bots Sanne L. Landman Martijn J. W. E. Rabelink Diana J. M. van den Wollenberg Rob C. Hoeben Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells Viruses pancreatic ductal adenocarcinoma oncolytic virus non-human primate adenovirus immunogenic cell death STING |
| title | Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells |
| title_full | Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells |
| title_fullStr | Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells |
| title_full_unstemmed | Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells |
| title_short | Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells |
| title_sort | immunostimulatory profile of cancer cell death by the adv lumc007 derived oncolytic virus goravir in cultured pancreatic cancer cells |
| topic | pancreatic ductal adenocarcinoma oncolytic virus non-human primate adenovirus immunogenic cell death STING |
| url | https://www.mdpi.com/1999-4915/15/2/283 |
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