A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy
Abstract Background Selectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity. Methods Herein, we simultaneously constructed five “armed” o...
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BMC
2022-04-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-022-01795-1 |
| _version_ | 1818278500265623552 |
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| author | Han Hu Siqi Zhang Linkang Cai Haixiao Duan Yuying Li Junhan Yang Yang Wang Biao Liu Shuang Dong Zhizheng Fang Binlei Liu |
| author_facet | Han Hu Siqi Zhang Linkang Cai Haixiao Duan Yuying Li Junhan Yang Yang Wang Biao Liu Shuang Dong Zhizheng Fang Binlei Liu |
| author_sort | Han Hu |
| collection | DOAJ |
| description | Abstract Background Selectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity. Methods Herein, we simultaneously constructed five “armed” oncolytic viruses (OVs), designated oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19. These OVs delete the ICP34.5 and ICP47 genes with the insertion of transgenes into the deleted ICP34.5 locus. The anti-tumor efficacy in vivo was tested in the syngeneic 4T1 and CT26 tumor-bearing mice model. Results The OVs showed comparable oncolytic capability in vitro. The combination therapy of oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19 exhibited the highest tumor inhibition efficacy compared with the treatment of single OV or two OVs combination. Conclusions The OVs armed with different transgenes combination therapy also named 5-valent oHSV2 (also called cocktail therapy) might be an effective therapeutic strategy for solid tumors. |
| first_indexed | 2024-12-12T23:18:25Z |
| format | Article |
| id | doaj.art-ba82300fc066418e99332913e5aa8487 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-12-12T23:18:25Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-ba82300fc066418e99332913e5aa84872022-12-22T00:08:22ZengBMCVirology Journal1743-422X2022-04-0119111210.1186/s12985-022-01795-1A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacyHan Hu0Siqi Zhang1Linkang Cai2Haixiao Duan3Yuying Li4Junhan Yang5Yang Wang6Biao Liu7Shuang Dong8Zhizheng Fang9Binlei Liu10National ‘‘111’’ Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of TechnologyWuhan Binhui Biopharmaceutical Co., Ltd.Wuhan Binhui Biopharmaceutical Co., Ltd.National ‘‘111’’ Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of TechnologyWuhan Binhui Biopharmaceutical Co., Ltd.National ‘‘111’’ Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of TechnologyNational ‘‘111’’ Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of TechnologyNational ‘‘111’’ Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of TechnologyHubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan Binhui Biopharmaceutical Co., Ltd.National ‘‘111’’ Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of TechnologyAbstract Background Selectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity. Methods Herein, we simultaneously constructed five “armed” oncolytic viruses (OVs), designated oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19. These OVs delete the ICP34.5 and ICP47 genes with the insertion of transgenes into the deleted ICP34.5 locus. The anti-tumor efficacy in vivo was tested in the syngeneic 4T1 and CT26 tumor-bearing mice model. Results The OVs showed comparable oncolytic capability in vitro. The combination therapy of oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19 exhibited the highest tumor inhibition efficacy compared with the treatment of single OV or two OVs combination. Conclusions The OVs armed with different transgenes combination therapy also named 5-valent oHSV2 (also called cocktail therapy) might be an effective therapeutic strategy for solid tumors.https://doi.org/10.1186/s12985-022-01795-1Oncolytic herpes simplex virusCombined therapy4T1CT26 |
| spellingShingle | Han Hu Siqi Zhang Linkang Cai Haixiao Duan Yuying Li Junhan Yang Yang Wang Biao Liu Shuang Dong Zhizheng Fang Binlei Liu A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy Virology Journal Oncolytic herpes simplex virus Combined therapy 4T1 CT26 |
| title | A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy |
| title_full | A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy |
| title_fullStr | A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy |
| title_full_unstemmed | A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy |
| title_short | A novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus-2 vectors armed with interleukin-12, interleukin-15, GM-CSF, PD1v, and IL-7 × CCL19 results in enhanced antitumor efficacy |
| title_sort | novel cocktail therapy based on quintuplet combination of oncolytic herpes simplex virus 2 vectors armed with interleukin 12 interleukin 15 gm csf pd1v and il 7 ccl19 results in enhanced antitumor efficacy |
| topic | Oncolytic herpes simplex virus Combined therapy 4T1 CT26 |
| url | https://doi.org/10.1186/s12985-022-01795-1 |
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