4-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal Adenocarcinoma
<b>Background:</b> Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a notably poor response to therapy due to its immunosuppressive tumor microenvironment (TME) and intrinsic drug resistance. The oncolytic virus (OV) represents a promising therapeutic strategy cap...
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MDPI AG
2024-11-01
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| author | Wenrui Gao Zhuoqian Zhao Ying Bi Jinghua Li Na Tian Cuizhu Zhang Shuyuan Pan Li Deng Yuntao Zhang |
| author_facet | Wenrui Gao Zhuoqian Zhao Ying Bi Jinghua Li Na Tian Cuizhu Zhang Shuyuan Pan Li Deng Yuntao Zhang |
| author_sort | Wenrui Gao |
| collection | DOAJ |
| description | <b>Background:</b> Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a notably poor response to therapy due to its immunosuppressive tumor microenvironment (TME) and intrinsic drug resistance. The oncolytic virus (OV) represents a promising therapeutic strategy capable of transforming the “cold” immunological profile of PDAC tumors to a “hot” one by reshaping the TME. 4-1BB (CD137), a crucial member of the tumor necrosis factor receptor superfamily, plays a significant role in T-cell activation and function. <b>Methods:</b> In this study, we constructed an oncolytic herpes simplex virus armed with 4-1BBL (oHSV-4-1BBL), the ligand for the 4-1BB receptor, and investigated its therapeutic effects in two mouse models of pancreatic cancer, Pan02_HVEM and KPC. <b>Results:</b> We found that oHSV-4-1BBL remarkably inhibited tumor growth and extended the median survival time in both models. To amplify the therapeutic effect, we further combined oHSV-4-1BBL with PD-1 antibody. This combination therapy not only further suppressed tumor growth but also extended the median survival time by an additional 11 days compared to oHSV (armed with GFP as a control) combined with PD-1 antibody treatment, with some mice achieving complete tumor regression. <b>Conclusions:</b> Our findings confirm the potential of combining oncolytic viral therapy with 4-1BB targeting in enhancing the treatment of pancreatic cancer. |
| format | Article |
| id | doaj-art-aaae0c2b7d2744ee8b3c4ebb9e2f1a89 |
| institution | DOAJ |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-aaae0c2b7d2744ee8b3c4ebb9e2f1a892025-08-20T02:57:04ZengMDPI AGVaccines2076-393X2024-11-011212130910.3390/vaccines121213094-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal AdenocarcinomaWenrui Gao0Zhuoqian Zhao1Ying Bi2Jinghua Li3Na Tian4Cuizhu Zhang5Shuyuan Pan6Li Deng7Yuntao Zhang8Beijing Institute of Biological Products Company Limited, Beijing 100176, ChinaCollege of Life Science, Nankai University, Tianjin 300071, ChinaBeijing Institute of Biological Products Company Limited, Beijing 100176, ChinaBeijing Institute of Biological Products Company Limited, Beijing 100176, ChinaBeijing Institute of Biological Products Company Limited, Beijing 100176, ChinaCollege of Life Science, Nankai University, Tianjin 300071, ChinaBeijing Institute of Biological Products Company Limited, Beijing 100176, ChinaBeijing Institute of Biological Products Company Limited, Beijing 100176, ChinaBeijing Institute of Biological Products Company Limited, Beijing 100176, China<b>Background:</b> Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a notably poor response to therapy due to its immunosuppressive tumor microenvironment (TME) and intrinsic drug resistance. The oncolytic virus (OV) represents a promising therapeutic strategy capable of transforming the “cold” immunological profile of PDAC tumors to a “hot” one by reshaping the TME. 4-1BB (CD137), a crucial member of the tumor necrosis factor receptor superfamily, plays a significant role in T-cell activation and function. <b>Methods:</b> In this study, we constructed an oncolytic herpes simplex virus armed with 4-1BBL (oHSV-4-1BBL), the ligand for the 4-1BB receptor, and investigated its therapeutic effects in two mouse models of pancreatic cancer, Pan02_HVEM and KPC. <b>Results:</b> We found that oHSV-4-1BBL remarkably inhibited tumor growth and extended the median survival time in both models. To amplify the therapeutic effect, we further combined oHSV-4-1BBL with PD-1 antibody. This combination therapy not only further suppressed tumor growth but also extended the median survival time by an additional 11 days compared to oHSV (armed with GFP as a control) combined with PD-1 antibody treatment, with some mice achieving complete tumor regression. <b>Conclusions:</b> Our findings confirm the potential of combining oncolytic viral therapy with 4-1BB targeting in enhancing the treatment of pancreatic cancer.https://www.mdpi.com/2076-393X/12/12/1309PDAConcolytic virusherpes simplex virus4-1BBLPD-1 |
| spellingShingle | Wenrui Gao Zhuoqian Zhao Ying Bi Jinghua Li Na Tian Cuizhu Zhang Shuyuan Pan Li Deng Yuntao Zhang 4-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal Adenocarcinoma Vaccines PDAC oncolytic virus herpes simplex virus 4-1BBL PD-1 |
| title | 4-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal Adenocarcinoma |
| title_full | 4-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal Adenocarcinoma |
| title_fullStr | 4-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | 4-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal Adenocarcinoma |
| title_short | 4-1BBL-Armed Oncolytic Herpes Simplex Virus Exerts Antitumor Effects in Pancreatic Ductal Adenocarcinoma |
| title_sort | 4 1bbl armed oncolytic herpes simplex virus exerts antitumor effects in pancreatic ductal adenocarcinoma |
| topic | PDAC oncolytic virus herpes simplex virus 4-1BBL PD-1 |
| url | https://www.mdpi.com/2076-393X/12/12/1309 |
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