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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
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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
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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
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Journal Article
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
2022
Overview
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.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
/ Animals
/ Biomedical and Life Sciences
/ Cancer
/ Colon
/ CT26
/ Enzymes
/ Genes
/ Genomes
/ Granulocyte-macrophage colony-stimulating factor
/ Granulocyte-Macrophage Colony-Stimulating Factor - genetics
/ Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use
/ Herpesvirus 2, Human - genetics
/ loci
/ Melanoma
/ Mice
/ Oncolytic herpes simplex virus
/ Oncolytic Virotherapy - methods
/ Oncolytic Viruses - genetics
/ Plasmids
/ Tumors
/ Virology
/ Viruses
