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.

Details

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
Author
Hu, Han  VIAFID ORCID Logo  ; Zhang, Siqi; Cai, Linkang; Duan, Haixiao; Li, Yuying; Yang, Junhan; Wang, Yang; Liu, Biao; Dong, Shuang; Fang, Zhizheng; Liu, Binlei
Pages
1-12
Section
Research
Publication year
2022
Publication date
2022
Publisher
Springer Nature B.V.
ISSN
1743-422X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s12985-022-01795-1
ProQuest document ID
2666649363
Copyright
© 2022. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.