PMID- 35459242 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220716 IS - 1743-422X (Electronic) IS - 1743-422X (Linking) VI - 19 IP - 1 DP - 2022 Apr 22 TI - 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 x CCL19 results in enhanced antitumor efficacy. PG - 74 LID - 10.1186/s12985-022-01795-1 [doi] LID - 74 AB - 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 x 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 x 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. CI - (c) 2022. The Author(s). FAU - Hu, Han AU - Hu H AUID- ORCID: 0000-0002-8188-6143 AD - 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 Technology, Wuhan, China. FAU - Zhang, Siqi AU - Zhang S AD - Wuhan Binhui Biopharmaceutical Co., Ltd., Wuhan, China. FAU - Cai, Linkang AU - Cai L AD - Wuhan Binhui Biopharmaceutical Co., Ltd., Wuhan, China. FAU - Duan, Haixiao AU - Duan H AD - 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 Technology, Wuhan, China. FAU - Li, Yuying AU - Li Y AD - Wuhan Binhui Biopharmaceutical Co., Ltd., Wuhan, China. FAU - Yang, Junhan AU - Yang J AD - 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 Technology, Wuhan, China. FAU - Wang, Yang AU - Wang Y AD - 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 Technology, Wuhan, China. FAU - Liu, Biao AU - Liu B AD - 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 Technology, Wuhan, China. FAU - Dong, Shuang AU - Dong S AD - Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Fang, Zhizheng AU - Fang Z AD - Wuhan Binhui Biopharmaceutical Co., Ltd., Wuhan, China. FAU - Liu, Binlei AU - Liu B AD - 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 Technology, Wuhan, China. liubl@hbut.edu.cn. AD - Wuhan Binhui Biopharmaceutical Co., Ltd., Wuhan, China. liubl@hbut.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220422 PL - England TA - Virol J JT - Virology journal JID - 101231645 RN - 0 (Interleukin-15) RN - 0 (Interleukin-7) RN - 187348-17-0 (Interleukin-12) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Genetic Vectors/genetics MH - Granulocyte-Macrophage Colony-Stimulating Factor/genetics/therapeutic use MH - Herpesvirus 2, Human/genetics MH - Interleukin-12/genetics MH - Interleukin-15/genetics MH - Interleukin-7/genetics MH - Mice MH - *Neoplasms/drug therapy MH - *Oncolytic Virotherapy/methods MH - *Oncolytic Viruses/genetics PMC - PMC9034647 OTO - NOTNLM OT - 4T1 OT - CT26 OT - Combined therapy OT - Oncolytic herpes simplex virus COIS- SZ, LC, YL, ZF, BL are employed by Wuhan Binhui Biopharmaceutical Co., Ltd. The authors would like to state clearly that there are no commercial conflicts with this work. EDAT- 2022/04/24 06:00 MHDA- 2022/04/27 06:00 PMCR- 2022/04/22 CRDT- 2022/04/23 05:12 PHST- 2021/08/26 00:00 [received] PHST- 2022/04/03 00:00 [accepted] PHST- 2022/04/23 05:12 [entrez] PHST- 2022/04/24 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/04/22 00:00 [pmc-release] AID - 10.1186/s12985-022-01795-1 [pii] AID - 1795 [pii] AID - 10.1186/s12985-022-01795-1 [doi] PST - epublish SO - Virol J. 2022 Apr 22;19(1):74. doi: 10.1186/s12985-022-01795-1.