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

基于溶瘤单纯疱疹病毒-2载体与白细胞介素-12、白细胞介素-15、GM-CSF、PD1v和IL-7×CCL19的五联组合的新型鸡尾酒疗法可增强抗肿瘤功效

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作者:Han Hu #, Siqi Zhang #, Linkang Cai, Haixiao Duan, Yuying Li, Junhan Yang, Yang Wang, Biao Liu, Shuang Dong, Zhizheng Fang, Binlei Liu

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.

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.

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.

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